Characterized by warm climate, small ice sheets and high sea level, past interglacials are quite relevant for a better understanding of our present-day warm climate and its future evolution. Investigating the response of climate system to different forcing factors, such as astronomical parameters, greenhouse gases (GHG) and ice sheets, could help better constrain the uncertainty of the sensitivity of the climate system and provide a basis for better understanding the internal climate processes and feedbacks. This thesis aims to perform a comprehensive and systematic investigation of the climate response in the two hemispheres to astronomical parameters, CO2 and Northern Hemisphere (NH) ice sheets during the interglacials of the past 800 ka mainly based on snapshot and transient simulations using the LOVECLIM model. The results show that the climate of the two hemispheres responds differently to astronomical parameters, CO2 and NH ice sheets. In terms of the effect of astronomical parameters, precession plays a dominant role on the Arctic sea ice, while obliquity plays a dominant role on the Southern Ocean sea ice. This is mainly related to the different geographical condition of the Arctic and the Southern Ocean and the related atmospheric and oceanic feedbacks. In the low latitudes of both hemispheres, SST shows a strong precession signal. However, in the mid and high latitudes, obliquity plays a dominant role on the Southern Hemisphere (SH) SST whereas precession is more important on the NH SST. This is largely due to the different response to insolation and feedbacks related to the different land-ocean distribution in the two hemispheres. The model results also show that the effect of CO2 on the SST in the mid-high latitudes is larger than in the low latitudes of both hemispheres, and CO2 plays a more important role on the SST at mid-high latitudes and sea ice in the SH than in the NH. The status of the Hudson Bay changed (closed or open) with the advance and retreat of the North American ice sheet. Therefore, before investigating the effect of the NH ice sheets on the climate, the effect of Hudson Bay closure on global and regional climate under different astronomical configurations was studied. The results show that the closure of the Hudson Bay could lead to a strengthening of the Atlantic Meridional Overturning Circulation (AMOC), which in turn leads to a warming in the NH with notable warming in the Labrador Sea and northeast North Atlantic, a cooling in the SH and a northward shift of the Inter-tropical Convergence Zone (ITCZ). In addition to the large-scale climate changes, the closure of Hudson Bay also leads to a strong cooling over the Hudson Bay region due to changes of surface properties and a cooling to the southeast of Greenland due to more wind-driven sea ice export from the Arctic. However, the effect of the Hudson Bay closure depends on background climate conditions, and it could weaken or slightly reinforce the effect of the ice sheets for different astronomical configurations. When the effect of the NH ice sheets is considered, the changes in Southern Ocean sea ice are highly and positively correlated with the NH ice volume, but the effect of the NH ice sheets on Arctic sea ice appears nonlinear, which depends on the size and location of the ice sheets as well as the NH summer insolation. The response of the mid-high latitude SST to the NH ice sheets is similar to the sea ice response in the same hemisphere. If the relative effect of insolation, CO2 and NH ice sheets is concerned, the NH mid-high latitude SST and sea ice are dominated by insolation, while the SH mid-high latitude SST and sea ice are dominated by ice sheets. Both CO2 and NH ice sheets play an important role in the SST at low latitudes of the two hemispheres. The half-precession cycles are systematically investigated based on both proxy records and transient simulations for the past interglacials. A compilation of available proxy records and the reanalysis of seven long, high-resolution records covering a wide region from Arctic to Antarctic, show that the half-precession signals are persistent and widely distributed at least over the last 800 ka, although their strength varies in time and regions. Our simulated results show that in response to the maximum equatorial insolation, the half-precession cycles can be simulated in the SST, surface air temperature (SAT) and precipitation near the Equator, and the half-precession signals in the tropics can be transported to the mid and high latitudes through oceanic circulations. The half-precession cycles can also be simulated in the grass fraction in the ‘Asian’ and ‘African’ monsoon regions due to vegetation feedbacks. Both eccentricity (and therefore precession) and obliquity can affect the strength of the half-precession signals. It is suppressed when eccentricity is small (leading to weak variation of precession) and obliquity variation is large, and vice versa. The half-precession signals are also weakened if the long-term variations of GHG and NH ice sheets are taken into account. Finally, the variations of the Arctic and Southern Ocean sea ice during the peak interglacials are investigated and compared with the sea ice of the present and future. The results show that the annual mean Arctic sea ice variation is primarily controlled by local summer insolation, while the annual mean Southern Ocean sea ice variation is more influenced by the CO2 concentration but the effect of local summer insolation can’t be ignored. The lowest Arctic sea ice area results from the highest summer insolation at MIS-15, and the lowest Southern Ocean sea ice area at MIS-9 is explained by the highest CO2 concentration and moderate local summer insolation. As compared to the present, the last nine interglacials all have much less sea ice in the Arctic annually and seasonally due to high summer insolation. They also have much less Arctic sea ice in summer than the double CO2 experiment, which makes to some degree the interglacials possible analogues for the future in terms of the changes of sea ice. However, compared to the double CO2 experiment, the interglacials all have much more sea ice in the Southern Ocean due to their much lower CO2 concentration, which suggests the inappropriateness of considering the interglacials as analogues for the future in the Southern Ocean. The results suggest that in the search for potential analogues of the present and future climate, the seasonal and regional climate variations should be considered.