To study the effect of Jiangu Shenjin Decoction on knee osteoarthritis via the Wnt/β-catenin signaling pathway.Methods:Forty-eight female Sprague-Dawley(SD) rats were randomly assigned into 6 groups(n=8):blank control，model，meloxicam tablets，Kanggu Zengsheng tablets，and medium-and high-dose Jiangu Shenjin Decoction.The rats in other groups except the blank control group were injected with papain in the knee joint cavity for the modeling of knee osteoarthritis.After successful modeling，the blank group and the model group received normal diet and water，and the rats in other groups were administrated with corresponding drugs by gavage for 4 weeks.The degrees of movement and knee swelling were observed.The serum levels of interleukin-1β(IL-1β)，interleukin-6(IL-6)，and tumor necrosis factor-α(TNF-α) were measured.The pathological changes in the articular cartilage were observed，and the mRNA levels of β-catenin and Wnt4 in the articular cartilage were examined.Results:The model group had higher levels of IL-1β，IL-6，and TNF-d than the blank control group，and the levels of the three inflammatory mediators had no significant differences between the meloxicam and Kanggu Zengsheng groups.Compared with the model group，the drug treatments lowered the levels of IL-1β，IL-6，and TNF-α.Moreover，the medium-dose Jiangu Shenjin Decoction group had lower levels of IL-1β，IL-6，and TNF-α than the high-dose group.The levels of IL-1β，IL-6，and TNF-α in the meloxicam and Kanggu Zengsheng groups were slightly higher than those in the medium-dose Jiangu Shenjin Decoction group.Compared with the blank control group，the model group showcased up-regulated mRNA level of Wnt4 and down-regulated mRNA level of β-catenin，and such changes were restored by drug treatments.The results indicated that Jiangu Shenjin Decoction was effective in regulating bone metabolism.Conclusion:Jiangu Shenjin Decoction may inhibit inflammatory mediators by regulating the expression of proteins in the Wnt/β-catenin signaling pathway，thereby influencing bone metabolism.