Objective To investigate the therapeutic effect of Bushentongluo recipe (BSTL) on bone destruction and its inhibiting effect on NF-κB/RANK/RANKL pathway in collagen-induced arthritis (CIA) rats. Methods SD rats were randomly divided into blank control group, CIA model group, methotrexate (MTX, 1 mg/kg) group, BSTL 0.5 g/kg and 2 g/kg groups, with 10 rats in each. Except the control group, the other rats were injected subcutaneously with type 2 collagen(Col2) at the base of the tail to establish CIA models. After exposure to MTX or BSTL recipe for consecutive 28 days, the pathological change of joint tissues was examined by HE staining. Immunohistochemistry was used to detect NF-κB p65 expression in synovial tissues. The cytokines and anti-Col2 levels were analyzed by ELISA. Western blotting was used to detect the expression of RANKL, RANK and osteoprotegerin (OPG) proteins. Results Compared with the CIA model group, the rats treated with 2 g/kg BSTL for 28 days had lower paw volume, arthritis index (AI), serum levels of IL-1β, IL-18, TNF-α, anti-Col2-IgG, anti-Col2-IgG2a, RANK and RANKL, and higher level of serum OPG. Besides, Western blotting showed that the expression of NF-κB p65, RANK and RANKL proteins decreased, but the expression of OPG protein increased in BSTL 2 g/kg group. Conclusion BSTL can alleviate the rheumatoid arthritis by down-regulating the expression of NF-κB p65, RANKL, RANK proteins, up-regulating OPG protein, and inhibiting systemic inflammation.