Objective To observe the effects of Semen Zizyphi Spinosae Decoction on the expression of Wnt-1 gene and potein in rats with depression models. Methods The chronic mild unpredictable stresses depression in rats models were replicated and divided into the control group， the model group， the fluoxetine group and the low， medium and high doseage of Semen Zizyphi Spinosae Decoction groups. The depression rat models were treated with Semen Zizyphi Spinosae Decoction and fluoxetine. The changes of body weight， sugar consumption and the score before and after the open field experiment were measured. Western blot and Realtime PCR were used to detect the expression of Wnt-1 protein and gene in hippocampus of rats. Results The depression models' weight gain slowed down. The scores of sugar consumption and the behavioral scores in openfield test decreased. The expression of Wnt-1 protein and gene in the hippocampus also decreased. After the treatment of Semen Zizyphi Spinosae Decoction， the body weight of the rats， sugar consumption and the score of open field experiment all increased. The expression of Wnt-1 protein and gene expression was up-regulated. Conclusions Semen Zizyphi Spinosae Decoction can increase the expression of Wnt-1 Protein gene and protein inhippocampus of rats with depression with the reduction of the neuronal cells' apoptosis， which has antidepressant effect.