〔Abstract〕 Objective Given that the PI3K/AKT/mTOR signaling pathway is associated with the progression of knee osteoarthritis(KOA), this study aims to investigate whether the polarization induction of synovial macrophages mediated by the PI3K/AKT/mTOR signaling axis is the cause of KOA progression. Methods The synovial fluid of KOA KL-Ⅱ and KL-Ⅲ patients and normal individuals was collected, and the percentage of M1 macrophages(CD80, CD86) and M2 macrophages(CD163, CD206) in the synovial fluid(M1/M2 ratio) was measured to evaluate the polarization of macrophage cytokines such as IL-1, IL-6, IL-10, and tumor necrosis factor(TNF)-α, transforming growth factor(TGF)-β Expression in KOA synovial fluid, and detect and analyze of key molecules PI3K/AKT/mTOR signaling axis PI3K, AKT3, mTORC1, and inducible nitric oxide synthase(iONS) in KOA synovial fluid. Results Compared with the synovial fluid of normal individuals, the percentage of M1 macrophages(CD80, CD86) in KOA patients increased(P<0.01), and the M1/M2 ratio increased(P<0.001); The expression of IL-1, IL-6, and TNF-α in the synovial fluid of the KOA group was also higher than that of the control group(P<0.01), while the expression of IL-10 and TGF-β in the KOA group was significantly reduced(P<0.01); The key proteins PI3K, AKT3, mTORC1, and downstream inflammatory factor iONS in the PI3K/AKT/mTOR signaling pathway in the synovial fluid of the KOA group were higher than those in the control group(P<0.01). Conclusion In KOA synovial fluid, M1 macrophage polarization plays a dominant role, and the inflammatory response mediated by M1 macrophage polarization may be the cause of synovitis. At the same time, the PI3K/AKT/mTOR signaling pathway may mediate the polarization of M1 macrophages involved in KOA inflammatory response.