Objective:To study the effects of Ganmai Dazao Decoction on the expression of brain-derived neurotrophic factor (BDNF) and serotonin transporter (SERT) genes in prefrontal lobe and amygdala and on the serum level of 5-hydroxytryptamine (5-HT) in depression model rats. Methods40 male Wistar rats were randomly assigned into normal group, model group, Ganmai Dazao Decoction group and fluoxetine hydrochloride group, 10 rats in each group. Except the normal group, the depression model was established by chronic unpredictable mild stress (CUMS) combined with orphaned method in the other groups. After modeling, Ganmai Dazao Decoction concentrate solution (12.5 ml/kg) was given to the Ganmai Dazao Decoction group, fluoxetine hydrochloride solution (10 ml/kg) was administered to the fluoxetine hydrochloride group and 2 ml of distilled water was given to the normal and model groups. All groups were treated for 28 days. The serum level of 5-HT in rats was detected by GC-MS; and the relative expression of BDNF mRNA and SERT mRNA in prefrontal lobe and amygdala was determined by real-time quantitative PCR.  Results:①The serum level of 5-HT and the relative expression of BDNF mRNA and SERT mRNA in prefrontal lobe and amygdala decreased in the model group compared to the normal group (P<0.05). ②Compared to the model group, the serum level of 5-HT increased in the Ganmai Dazao Decoction and fluoxetine hydrochloride groups (P<0.05); the relative expression of BDNF mRNA in prefrontal lobe increased in the Ganmai Dazao Decoction group (P<0.05) and the relative expression of BDNF mRNA and SERT mRNA in prefrontal lobe increased in the fluoxetine hydrochloride group (P<0.05); and the relative expression of BDNF mRNA and SERT mRNA in amygdala increased in the Ganmai Dazao Decoction and fluoxetine hydrochloride groups (P<0.05). ③There were no statistically significant differences in the serum level of 5-HT and the relative expression of BDNF mRNA and SERT mRNA in prefrontal lobe and amygdala between the Ganmai Dazao Decoction group and the fluoxetine hydrochloride group (P>0.05).  Conclusion:Ganmai Dazao Decoction may treat depression by increasing the serum level of 5-HT and the expression of BDNF mRNA in prefrontal lobe and amygdala and SERT mRNA in amygdala.