ObjectiveTo investigate the effect of Kaixin-San (KXS) on behavior, brain monoamine transmitters, and hippocampal brain-derived neurotrophic factor (BDNF) in mice receiving tail suspension test (TST), so as to explore the correlation of the antidepressant effect of KXS and hippocampal BDNF level. MethodsThe effect of KXS on the immobility time of mice in the TST was observed. The levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in the brain were determined by high-performance liquid chromatography (HPLC). Western blotting analysis was used to examine the expressions of cAMP-response element-binding protein (CREB), p-CREB, and BDNF in the hippocampus. BDNF mRNA expression was also examined by RT-PCR. Pearson’s correlation analysis was used to evaluate relationship between anti-depression effect of Kaixin-San and hippocampal BDNF level. ResultsKXS reduced the immobility time of mice in the TST (P＜0.05); it also increased the brain levels of monoamine transmitters (DA and 5-HT) and hippocampal levels of CREB, p-CREB and BDNF compared with the control mice(P＜0.05). Moreover, the anti-depression effect of KXS was correlated with BDNF level (protein:r=-0.694, P＜0.01; mRNA:r=-0.547, P＜0.01) in the hippocampus. ConclusionThe anti-depression effect of KXS is positively correlated with the hippocampal BDNF level, indicating KXS may exert anti-depression effect via increasing hippocampal BDNF.