Objective: To observe the anti-inflammatory effect of electroacupuncture on collagen-induced arthritis in rats and to explore the molecular mechanisms of vasoactive intestinal peptide (VIP) in mediating electroacupuncture  Methods: Fifty male Sprague Dawley rats were randomly divided into five groups, with 10 rats in each group.Except for the normal saline (NS) group and electroacupuncture group, CIA rat models were established by collagen II.CIA models were induced by collagen type II.Normal saline group and model group were not intervened.Electroacupuncture group and electroacupuncture plus VIP receptor antagonist group, and electroacupuncture plus normal saline group were treated with electroacupuncture at Zusanli (ST-36) and Xuanzhong (GB-39).VIP receptor antagonist was injected before electroacupuncture three times a week, for 4 weeks.Scores of arthritis indexes were recorded during the electroacupuncture intervened period.The pathologic condition of synovial tissues was observed by HE.Expression of VIP was observed by immunohistochemical method, and expressions of serum VIP, IFN-γ and IL-4 were detected by ELISA  Results: After intervention, the arthritis scores in electroacupuncture group were lower than that of the model group and electroacupuncture plus VIP receptor antagonist group.H  Results: showed that there were inflammatory cells infiltration and fibroblasts proliferation in electroacupuncture group, and were lower than that of the model group.Immunohistochemisty showed that the VIP expression on synovial tissues in electroacupuncture group was significant higher than that of the model group, electroacupuncture plus VIP receptor antagonist group.Expression of VIP and IL-4 in electroacupuncture group were higher than that of the model group and electroacupuncture plus VIP receptor antagonist group (P<0.05, P<0.01); IFN-γ expression in the electroacupuncture group was lower than that of the model group and electroacupuncture plus VIP receptor antagonist group (P<0.05)  Conclusion: Electro-acupuncture on Zusanli (ST-36) and Xuanzhong (GB-39) shows significant inhibition role of arthritis in CIA rats.Its mechanism may be associated with up-regulating the IL-4 expression and down-regulating the IFN-γ expression.