〔Abstract〕 Objective To investigate the changes of serum interleukin-15(IL-15) in patients with knee osteoarthritis(KOA) and healthy controls. Methods The peripheral blood of 30 KOA patients and the peripheral blood of 35 healthy adults were selected. The KOA group was divided into two groups, one was the experimental group with IL-15(10 ng/ml), and the other was without IL-15 as the control group. The HC group was also divided into two groups, one was the experimental group with IL-15(10 ng/ml), and the other was without IL-15 as the control group. ELISA method was used to detect the level of IL-15 in peripheral blood of KOA group and healthy control group. Flow cytometry was used to detect the effect of IL-15 on the expression of natural killer( NK) cell receptor in peripheral blood of patients with KOA and healthy controls,and the ELISA method was used to detect the effect of IL-15 on the levels of tumor necrosis factor α( TNF-α) and interferon γ( IFN-γ) by peripheral blood mononuclear cells( PBMCs). Results The level of serum IL-15 in KOA group was higher than that in control group. IL-15 could enhance the expression of NK cell receptors CD69,CD94 and NKG2 D in KOA group. The levels of TNF-αand IFN-γ in the supernatant of KOA group were higher than those of control group. Conclusion IL-15 antagonist may become a new treatment option to prevent or delay the progression of KOA.