Objective:To observe the effect of norcantharidin (NCTD) on collagen-induced arthritis (CIA) rats.Methods:Sixty Sprague-Dawley(SD) rats were randomly divided into 6 groups (n=10):normal group,CIA model group(model group),NCTD low-dose group [1.35 mg/(kg·d)],NCTD middle-dose group [2.7 mg/(kg·d)],NCTD high-dose group [5.4 mg/(kg·d)] and methotrexate (MTX) group [1.8 mg/(kg/w)].Anesthetized rats were sacrificed by luxation of cervical vertebra after 4 weeks of administration.The arthritis scores were evaluated twice a week.The pathological changes in the ankle joints of rats were observed by hematoxylin-eosin (H&E) staining.The serum levels of interleukin (IL) 1 β,IL-6,tumor necrosis factor (TNF)-α,vascular endothelial growth factor (VEGF),IL-17 and transform growth factor (TGF) β were detected by enzyme linked immunosorbent assay (ELISA).The mRNA expression of retinoid-related orphan nuclear receptor γt (RORy t) and forkhead box P3 (Foxp3) in peripheral blood lymphocytes were confirmed by real-time polymerase chain reaction.Results:MTX and high-dose NCTD not only decreased the arthritis scores but also alleviated the pathological changes in CIA rats\' ankle joints compared with the model group (P＜0.05 or P＜0.01).All doses of NCTD significantly inhibited the serum levels of IL-6,IL-17 and TNF-α in CIA rats (P＜0.05).Only middle-and high-dose of NCTD prominently decreased serum IL-1 β and TGF-β levels of CIA rats (P＜0.05).However,NCTD has no effect on vascular endothelial growth factor (VEGF) level in CIA rats.The Foxp3 mRNA expression in all NCTD groups were increased significantly than in the model group (P＜0.05).The mRNA expression of ROR γt in NCTD high-dose group was decreased apparently in comparison with the model group (P＜0.05).Conclusion:NCTD showed therapeutic effect on CIA rats by inhibition of cytokines and regulation of Th17/Treg cells.