Abstract: OBJECTIVE To study the rapid antidepressant effect of Yueju Ganmai Dazao Decoction (Yuegan Decoction， YG) on postpartum depression (PPD) mice， and to explore the pathogenesis of PPD and the mechanism of Chinese medicine from BDNF-TrkB pathway. METHODS 40 Balb/c female mice were randomly divided into two groups. The control group was not given any stimulation. The pre-pregnancy stressed group was subjected to chronic restraint stress. After 3 weeks， the mice in the pre-pregnancy stress group were mated. The mice were arranged for sucrose preference test (SPT) and forced swim test（FST） 3 weeks after delivery. The PPD mice induced by the pre-pregnancy stress were randomly divided into three groups: model group， YG group and ketamine group. The intervention effect of YG on the mice was detected， and the prefrontal lobes of the mice were taken to detect the expression of BDNF， TrkB， p-GSK3β and GSK3β protein. RESULTS After 3 weeks postpartum， the model mice showed depression-like behaviors. Reduced preference in drinking sucrose solution were found in SPT (P<0.01)， and immobility in FST was significantly increased (P<0.01). And the expressions of BDNF， TrkB and p-GSK3β/GSK3β in the prefrontal lobe of the PPD model group were significantly reduced (P<0.05)， compared to control group. Acute YG improved performance in the SPT and FST (P<0.01)， which was similar to ketamine. A single dose of YG or ketamine normalized BDNF-TrkB signaling in the PPD model mice (P<0.05). CONCLUSION Chronic pre-pregnancy stress induces postpartum depression-like symptoms in Balb/c mice. The pathogenesis may be related to activation of the prefrontal BDNF-TrkB pathway. The rapid antidepressant effect of YG on PPD model mice may be related to the improvement of the prefrontal BDNF-TrkB signaling pathway.