Abstract: To investigate the therapeutic effect and mechanism of sodium formononetin-3′-sulphonate (SFS) on collagen-induced rheumatoid arthritis in mice, C57 mice were induced with chicken type II collagen to establish a model of rheumatoid arthritis (collagen-induced arthritis, CIA), and were injected intraperitoneally with different doses of SFS (50,100,200 mg/kg). Body weight, food intake and foot swelling of all groups were observed during the experiment.After the treatment, TNF-α, IL-6, and IL-10 in the serum were detected with the CBA kit; NF-κB p65, p-NF-κB p65 (p-p65), TIPE2, PCNP and IκB-α in spleen tissue were determined by Western blot; the organ index, pathological changes of ankle joint cartilage tissue and the positive expression of NF-κB p65 in ankle joint tissue were also observed.The results showed that, compared with the model group, the body weight and food intake of mice in the treatment group increased, while the degree of foot swelling decreased; the expression levels of inflammatory factors TNF-α and IL-6 in serum decreased, while the expression of anti-inflammatory factor IL-10 increased; the expression levels of NF-κB p65, p-p65 and PCNP in spleen tissue decreased, while the expression of TIPE2 and IκB-α protein increased; the index of spleen and thymus of the CIA mice in the treatment group, the infiltration of inflammatory cells in the ankle joint, the destruction of synovial tissue and cartilage, and the positive expression of NF-κB p65 decreased.Among them, the high-dose group of SFS showed a better therapeutic effect.It is suggested that SFS has a therapeutic effect on CIA mice, and the mechanism may be achieved by regulating the NF-κB p65 signaling pathway and inhibiting the expression of inflammatory factors.