Abstract: Objective: To investigate whether acupuncture treats knee osteoarthritis (KOA) by inhibiting the ferroptosis process. Methods: Eighteen SPF-grade male SD rats were selected and randomly divided into the shamoperation group,the model group,and the experiment group,with six rats in each group. The sham-operation group received an intra-articular injection of an equal volume of 0.9% sodium chloride solution; the model group was subjected to the sodium iodoacetate method to establish the KOA model; the experiment group received acupuncture starting from the second day after modeling, with Zusanli (ST36), Neixiyan (EX-LE4), and Heding (EX-LE2) points selected. Acupuncture was administered five days per week,30 min per session,for three consecutive weeks. During the experiment,the von Frey filament test was used weekly to assess pain response,body weight was measured with a balance,and knee joint width was measured with a vernier caliper. After the experiment,knee joint tissues were collected for hematoxylin-eosin staining, safranin O-fast green staining, TUNEL apoptosis detection, and immunofluorescence double staining to observe the co-localization of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4),and chondrocyte marker SOX9. Blood and synovial fluid were collected to measure the expression levels of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor- α (TNF- α), and interleukin-1β (IL-1β) by enzyme-linked immunosorbent assay. Cartilage tissues were collected to determine the contents of glutathione (GSH) and ferrous ion (Fe2+). Results:Compared with the sham-operation group,the model group showed a significant decrease in pain response,a gradual reduction in body weight,and an increase in knee joint width. In the model group, articular cartilage cells were disorganized and clustered, with partial chondrocyte loss, uneven matrix staining, destruction of cartilage structure, irregular surface, and blurred cartilage layers; cartilage erosion was evident. Compared with the model group, the experiment group showed an increased mechanical paw withdrawal threshold( reduced hyperalgesia),a significant increase in body weight,and a decrease in knee joint width. The pathological damage and cartilage erosion in the knee joint cartilage of the experiment group were significantly alleviated compared with those in the model group. Compared with the sham-operation group, the expression of inflammatory factors IL-6, IL-1β, and TNF- α in serum and synovial fluid, as well as the count of apoptotic chondrocytes in the knee joint,were significantly increased in the model group. In the knee joint cartilage of the model group, the expression levels of SLC7A11 and GPX4 co-localized with SOX9 were reduced, GSH content was increased, and Fe2+ content was decreased, with all differences being statistically significant (P<0.05). Compared with the model group,the expression of inflammatory factors IL-6,TNF-α,and IL-1β in blood and synovial fluid, as well as the count of apoptotic chondrocytes in the knee joint,were significantly reduced in the experiment group. In the knee joint cartilage of the experiment group, the expression of GPX4 and SLC7A11 co-localized with SOX9 was increased, GSH content was increased, and Fe2+ content was decreased, with all differences being statistically significant (P<0.05). Conclusion:Acupuncture can alleviate pain,improve body weight and knee joint width,and reduce cartilage tissue damage in KOA rats by regulating the expression of inflammatory factors, promoting the colocalization of SLC7A11 and GPX4 with chondrocyte marker SOX9, and modulating the contents of GSH and Fe2+ in cartilage tissue,thereby inhibiting ferroptosis.