Objective: To study the regulatory effect of feilongzhangxue on the levels of HMGB1-TLR4 / RANKL-NF-?B signaling pathway related factors HMGB1, RANKL, rank, TRAF-6 and NF-?Bp65 in osteoclasts, so as to explore the mechanism of feilongzhangxue intervention in RA; Methods: The osteoclasts with good activity were randomly divided into blank group, methotrexate control group and Zhuang medicine feilongzhang blood containing serum treatment group, which were divided into OC + blank group, OC + methotrexate control group, OC + Zhuang medicine feilongzhang blood containing serum group; The expression of HMGB1, RANKL, rank, TRAF-6 and NF-?Bp65 mRNA was detected by RT-PCR; The protein expressions of HMGB1, RANKL, RANK, TRAF-6 and NF-?Bp65 were detected by immunofluorescence. Results: PCR results showed that: Compared with the blank group, feilongzhangxue could effectively inhibit the expression levels of HMGB1, RANKL, rank, TRAF-6 and NF-? B p65 mRNA in OC cells, and the inhibitory effect was stronger than methotrexate. Immunofluorescence test results showed that: Compared with the blank group and methotrexate group, feilongzhangxue could effectively inhibit the protein expression of HMGB1, RANKL, rank, TRAF-6 and NF - ? B p65 in OC cells. Conclusion: The effect of Zhuang medicine feilongzhangxue on hmgb1-tlr4 / rankl-nf - ? B signaling pathway of osteoclasts is through the regulation of related factors HMGB1, RANKL, rank, TRAF-6 and NF-?Bp65, which may be the key mechanism of Zhuang medicine feilongzhangxue on rheumatoid arthritis.