To observe the effects of Xiaoyaosan Decoction on the expression of Belin-1 and LC3 in hippocampus of rats with depression induced by chronic restraint stress. Methods:A total of 20 Wistar rats were randomly divided into 4 groups:the control group, the model group, the Xiaoyaosan (XYS) group and the fluoxetine group. Depression model was established by 21-day chronic restraint stress, and the expression of Belin-1 and LC3 in CA3 of rats’ hippocampus was detected by immunohistochemistry. Results:There is significant differences between the control group and other groups (P<0.05). Xiaoyaosan Decoction could down-regulated the expression of Belin-1 and LC3 (P<0.05). Conclusion:The expression of Belin-1 and LC3 in hippocampus of rats with depression induced by chronic restraint stress indicated that autophagy may be part of the mechanism of depression. The effect of Xiaoyaosan Decoction on depression could be related to the regulation of Belin-1 and LC3.