Objective: To observe the effects of electro-acupuncture(EA)on ERK signal pathway in the brain of depression rats model induced by chronic stress, and to explore the molecular mechanism of acupuncture in treating depression. Methods: 32 SD rats were randomly divided into 4 groups: control group, model group, ER group, and fIuoxetine hydrochloride group. The method of chronic stress combined with solitary condition was adopted to make rats model. The rats of ER group were acupunctured on acupoints of Baihui(GV 20) and Yintang(EX-HN 3) with electro-acupuncture. The rats of fIuoxetine hydrochloride group were gavaged with fIuoxetine hydrochloride. Western blot was used to detect the level of Ras, c-raf, p-craf, ERK and p-ERK in the hippocampus of rats. Results: There was no significant difference among all the groups in the level of Ras, c-raf, p-c-raf and ERK. The level of p-ERK in the hippocampus in the model group was significantly lower than that in the control group(P0.05). Compare with model group, the level of p-ERK with the EA group and the l uoxetine group increased significantly(P0.05). Conclusion: EA could improve the phosphorylation of main signals in ERK pathway in the brain of depression model rats.