〔Abstract〕 Objective To study the effect of chronic unpredictable stress(CUS) on the sexual behavior of mice and its possible molecular mechanism. Methods 20 male C57 BL/6 J mice were divided into two groups randomly: control group(n=10) and CUS group(n=10), and the weight of the mice between the two groups was balanced. The control group was 3-5 mice per cage and normal feeding. CUS group was subjected to 21 days CUS combined with single cage fed to establish a depression model. After 21 days, the depressive-like behaviors of the two groups were tested by sucrose preference test and forced swimming test. Then the sexual behavior was detected by olfactory preference test and female urine sniffing test, and the protein and mRNA expression of brain-derived neurotrophic factor(BDNF) in ventral tegmental area(VTA) were detected. Results CUS could significantly decrease sucrose preference(P<0.05) and increase the immobility time in the forced swim test(P<0.05)compared to control mice, indicating depression-like behavior in mice, and impaired sexual behavior in the olfactory preference test(P<0.05)and female urine sniffing test(P<0.05)in mice, and decreased the expression of BDNF in VTA brain regions. The difference was statistically significant. Conclusion The impaired sexual behavior of mice induced by CUS may be related to the decreased expression of BDNF in VTA brain regions. The BDNF signaling pathway may be involved in the regulation of impaired sexual behavior of mice induced by CUS.