Abstract: Objective： To discuss the activation of brain regions in mice under forced swimming stress. Methods： 11 healthy wild-type C57 mice of 6-8 weeks were randomly divided into the stress group（FS，n=5） and the control group (Ctl，n=6).The mice in the FS group were given ice water bath forced swimming stimulation， but the Ctl group did not.Then， the number of c-fos positive cells in brain regions was counted to estimate the activation of mice brain regions after forced swimming in ice water bath. Results： The number of c-fos positive cells in the medial prefrontal lobe (mPFC： Cg1， PrL， IL)， amygdala (amygdala： BLA， BMA)， and nucleus accumbens (NAc) were higher in the FS mice than in the Ctl mice. The number of c-fos positive cells in the FS mice in the hippocampus brain area was lower than that in Ctl， and the hippocampal gyrus (CA) FS mice were lower than Ctl， while the dentate gyrus (DG) FS mice had no significant difference from Ctl. There was no significant difference in c-fos expression between FS and Ctl mice in the piri-like cortex (Pir). Conclusion： Under the ice water bath forced swimming stress， the activation of brain regions in the mice involved the medial prefrontal cortex， amygdala， nucleus accumbens， but the expression of hippocampal was decreased， while the piriform cortex (Pir) did not participate in the activation， suggesting that the above several brain regions participated in the depression-like behavior caused by forced swimming in the ice water bath.