Objectives: The purpose of this study was to examine the anti-depressive effects of BanHaHuBakTang-kami (BHHBT) on an animal model of depression induced by chronic immobility stress. Methods: Mice were treated daily with immobilization stress for 2 hours over a period of 21 days. To examine the effect of BHHBT, we performed behavioral, biochemical and histological analysis to measure immobility time (FST), brain neurotransmitter concentration (HPLC, ELISA), hippocampal damage (H&E staining) and CRF-R1 expression (immunohistochemistry). Results: BHHBT has reduced the immobility time of immobilization stress exposed mice in the forced swimming test. BHHBT has increased the amount of serotonin in the brain. BHHBT has increased the expression level of serotonin in the brain. BHHBT 540 mg/kg were sufficient to prevent tissue damage in the hippocampus region. BHHBT has reduced the expression level of CRF receptors in the hippocampus region. Conclusions: These results suggest that BHHBT may have anti-depressive effects on mice treated with immobilization stress by reducing immobility, increasing brain serotonin concentration and reducing CRF-R1 expression in the hippocampus region.