Abstract: OBJECTIVE To observe the protective effect of Ruyi Zhenbao pill on rat with sciatic nerve chronic constriction injury(CCI) and explore the effect on cytokine levels. METHODS Eligible male SD rats were screened by thermal withdraw latency(TWL). The sciatic nerve trunk was surgically isolated after anesthesia. The proximal end of the three branches of sciatic nerve was ligated by 4-0 chromium-containing enteric line for four times, with the interval of about 1 mm between each node, to replicate the model of chronic neuropathic pain. The 45 rats with successful modeling were randomly divided into 5 groups, 9 in each group, the groups were model control group, Ruyi Zhenbao pills low(0.5 g·kg^-1), middle(1.5 g·kg^-1), high(4.5 g·kg^-1) dose group, rotundine group(18 mg·kg^-1). And set up a sham-operated control group. The corresponding drug or solvent was administered by intragastric once a day for 10 consecutive days. TWL was measured 30 min after administration on days 5, 7, and 10. On the 11th day, blood was collected from the abdominal aorta and cytokine levels were measured. RESULTS TWL of rats in Ruyi Zhenbao pill low, middle, high dose group and rotundine group was obviously prolonged, and the content of IL-10 was obviously decreased. The content of TNF-α in the serum of rats in Ruyi Zhenbao pill high dose group and rotundine group was obviously decreased. CONCLUSION Ruyi Zhenbao pill may regulate the level of cytokines, alleviate the pain inflammatory cascade, inhibit central nervous system sensitization, and play a protective role in the chronic neuropathic pain caused by sciatic nerve CCI.