Objective:To determine the mechanisms underlying the anti-depressant effects of Kaixin Jieyu Decoction(开心解郁汤,KJD)by investigating the effects of KJD on behavior,monoamine neurotransmitter levels,and serotonin(5-HT)receptor subtype expression in the brain in a rat model of depression.Methods:The rat depression model was established using chronic unpredictable mild stress(CUMS).Forty-eight Sprague Dawley rats were randomly divided into control,depression model(CUMS),CUMS±KJD(7.7 g/kg^(-1)·d^(-1)of crude drug),and CUMS+fluoxetine(2.4 mg/kg^(-1)·d^(-1))groups(n=12 in each group),and the treatments lasted for 21 days.We regularly evaluated body weight,sucrose consumption,and horizontal and vertical activity scores in open-field tests.The content of the monoamine neurotransmitters 5-HT,norepinephrine(NE),and dopamine(DA)and the DA metabolite homovanillic acid in the cerebral cortex,and 5-HT_(1A)and 5-HT_(2A)receptor mRNA in the cerebral cortex and the hippocampus,were determined respectively by high-performance liquid chromatography-coularray electrochemical detector and real-time polymerase chain reaction.Results:Compared with the control group,CUMS rats showed a variety of depression-like behavioral changes,including a significant reduction in body weight,sucrose consumption,and horizontal and vertical activity scores in open-field tests(P<0.05 or P<0.01),and a significant decrease in 5-HT and NE levels and 5-HT_(2A)receptor mRNA expression.In contrast,they showed a significant increase in 5-HT_(1A)receptor mRNA expression in the cerebral cortex.In the hippocampus,5-HT_(1A)receptor mRNA expression was lower whereas 5-HT_(2A)receptor mRNA expression was higher than in the control group(P<0.05 or P<0.01).Treatment with KJD or fluoxetine partially attenuated these changes(P<0.05 or P<0.01).Conclusion:KJD could normalize the levels of 5-HT and NE and adjust the balance of 5-HT_(1A)and 5-HT_(2A)receptor expression in rat cerebrum,and this may be one of mechanisms of antidepressant effects of KJD.