Objective To investigate the role of high-mobility group box-1 (HMGB1) in the pathogenesis and the treatment of rheumatoid arthritis (RA) and the pathogenesis of TWP in treatment of RA.Methods A rat model of collagen induced arthritis (CIA) was developed and CIA rats were divided into the model group, the TWP group, the MTX group and the combination treatment group. And the tissues and blood were drawn from the rats 4 weeks later. HMGB1 expression in synovium, joint and the sera were tested by immunohistochemical stain and ELISA. Results HMGB l expression of the model in the synovium, joint and serum [(23.8±2.2) ng/ml] were remarkably higher than the control [(7.4±1.6) ng/ml] (P<0.01); HMGB1 expression of the treatment groups in synovium, joint and serum [ (13.3±3.1), (17.4±4.9), (11.7±1.5 ) ng/ml]is obviously lower than the model (P<0.01), and were higher than that of the controls(P<0.05). Conclusion HMGB1 participates in the hyperplasia of synovial membrane, cartilage and bone destruction of CIA. The molecular mechanism for the TWP and MTX in the trentment of synovitis and bone destruction of RA is correlated with the expression of HMGB1.