Objective:To investigate the antidepressant-like effects of Chaihu Shugan Powder (CSP,柴胡疏肝散) and to explore its underlying mechanisms.Methods:Thirty-two Sprague-Dawley rats were randomly divided into control (CON),chronic unpredictable mild stress (CUMS),fluoxetine (FLU),and CSP groups,8 rats in each group.All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model.The open field test (OFT),forced swimming test (FST),and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP.Terminal deoxynucleotidyl transferase(TdT) dUTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues.The mRNA and protein levels of glucose-regulated protein (GRP) 78,spliced X-box-binding protein (XBP)-1,CCAAT/enhancer-binding protein homologous protein (CHOP),caspase-12,and c-Jun N-terminal kinase (JNK) in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis,respectively.Results:Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats,as revealed by enhanced time and distance in the center of the OFT (P＜0.05),an increased preference for sucrose,and longer swimming time and shorter immobility time during the FST (all P＜0.05).In addition,CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons (P＜0.05).The mRNA and protein expression levels of GRP78,spliced XBP-1,and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins (all P＜0.05),whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats.Conclusion:CSP can improve depression-like behavior in rats exposed to CUMS,possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.