Abstract: OBJECTIVE To explore the effect of proanthocyanidin on unpredictable chronic mild stress(UCMS) mice with depression-like behavior, and its effect on the content of monoamine. METHODS ICR mice were divided into 6 groups:blank group, UCMS group, proanthocyanidin low, medium, high dose groups(UCMS+proanthocyanidin 12.5, 25 and 50 mg·kg^-1), fluoxetine group(UCMS+fluoxetine 10 mg·kg^-1). The model of mice was established by UCMS, and then to evaluate depression-like behavior and anxiety-like behavior. The content of monoamine in the hippocampus, cortex and hypothalamus was determined by HPLC. RESULTS Compared with the control group, the duration of immobility of UCMS mice in the tail suspension test significantly increased(P<0.05), the number of the buried marble of UCMS mice increased(P<0.01). The expression of norepinephrine(NE), 5-hydroxytryptamine(5-HT) and dopamine(DA) decreased in the hippocampus, prefrontal cortex and hypothalamus of UCMS model group as compared with those in the control group. Proanthocyanidin improved the behavior of UCMS mice, and reversed the levels of 5-HT, NE and DA in the hippocampus, prefrontal cortex and hypothalamus. CONCLUSION UCMS model mice have abnormal change in the depression and anxiety-like behavior and expression of monoamine in the hippocampus, prefrontal cortex and hypothalamus. Proanthocyanidin can ameliorate the changes of the behavior and regulate the expression of monoamine in the hippocampus, prefrontal cortex and hypothalamus.