To observe the effect of Minor Bupleurum Decoction on monoamine neurotransmitters in brain tissue of rat model of depression, and to investigate the mechanism of antidepression of Minor Bupleurum Decoction. Methods: Rat model of depression built by chronic restraint stress was used to observe the behavioral changes of Minor Bupleurum Decoction. HPLC method was used to determine the content of monoamine neurotransmitters in brain of rats. And then the effects of Minor Bupleurum Decoction and other Chinese medicinals were evaluated on animal models of depression. Results: The contents of monoamine neurotransmitters, model group and the normal group were significantly different. The content of 5-HT, NE, 5-HIAA significantly increased in the Quan Fang group. The content of NE in the hippocampus of the Jiang Xia group and the Shen Cao group significantly increased. And the content of 5-HT also significantly increased in Quan Fang group, Chai Qin group, Shen Cao group. Moreover, the content of 5-HIAA in the hippocampus of the Quan Fang group, Chai Qin group and Jiang Xia group significantly increased. Conclusion: Minor Bupleurum Decoction has a good therapeutic effect on depression, each of the drugs on the role of brain tissue in rats with the target point of the neurotransmitter has a certain focus. Bupleurum and Scutellaria have antidepressant effects by increasing the content of 5-HT in rat hippocampus. Pinellia and ginger could significantly increase hippocampal NE content. Although the effects of the 5-HT were not significant, but it could significantly increase the content of 5-HT degradation of 5-HIAA; Ginseng, l Liquorice Root, and Chinese Date could significantly elevate the condition of depression 5-rat brain HT and NE content.