Objective To explore the possible mechanism of Baidizao Mixture（百地枣合剂） in treating depression. Methods A total of 60 Wistar rats were randomly divided into a blank group

a model group

a fluoxetine hydrochloride group and a Baidizao Mixture high

medium and low dose groups

with 10 rats in each group. Except the blank group

rats were treated with chronic stress stimulation and orphanage for 29 days to establish a depression rat model. Beginning on the 8 th day of the experiment

the low

medium and high doses of Baidizao Mixture were given Baidizao Mixture at a concentration of 0.7

1.4

and 2.8 g/ml respectively

and the fluoxetine hydrochloride group was given a concentration of 0.36 mg/ml fluoxetine hydrochloride suspension. The model group and the blank group were given normal saline

and all groups were given intragastric administration with 1 ml/100 g body weight for 21 consecutive days. On the baseline

7 th

and 29 th day of the experiment

rats in all groups were subjected to an open field test and a sugar water preference test. The horizontal movement distance and standing times of the rats were observed. The sugar water preference rate was caculated. The Nissl stain was used to observe the hippocampal histopathology of the rats. Glycogen synthase kinase 3β（GSK-3β） mRNA and β-catenin expression in hippocampus were detected. Results On the 29 th day of the experiment

compared with the blank group

the horizontal movement distance and the number of standing of rats in the model group decreased

the sugar water preference rate decreased

the β-catenin protein expression in the hippocampus tissue decreased

and GSK-3β mRNA expression increased（P<0.05 or P<0.01）; Compared with the model group

the rats in the fluoxetine hydrochloride group and the Baidizao Mixture high dose group increased horizontal movement distance and standing times

increased sugar water preference

increased β-catenin protein expression in hippocampus

and reduced GSK-3β mRNA（P<0.05 or P<0.01）. The sugar and water consumption rate and β-catenin protein expression in hippocampus of the high dose Baidizao Mixture group were increased than those in the medium-dose and low-dose Baidizao Mixture group（P<0.01）. Conclusion Baidizao Mixture can improve the behavior of depressive rats. The mechanism may be related to reducing GSK-3β mRNA and increasing β-catenin expression in hippocampus

and the high dose group showed the best result.