Osteoarthritis (OA) remains a challenge for clinicians and effective treatments are lacking. In this study, we investigated JNK/NF-kappa B signaling in knee OA patients. Rats were used to establish an OA model and were divided into six groups; (1) Control (sterile saline injection only); (2) Controls with treadmill exercise (treadmill); (3) Controls with wheel exercise (wheel); (4) OA (MIA injection); (5) OA with treadmill exercise (OA + treadmill); and (6) OA with wheel exercise (OA + wheel). The results showed that, compared to the OA group, the OA + treadmill and OA + wheel groups had lower levels of IL-1 beta, IL-6 and TNF-alpha, and similar levels of p-P65, p-JNK, and P-l kappa B alpha. Furthermore, treatment with the JNK agonist anisomycin enhanced the damage to the joint cartilage and increased the levels of IL-1 beta, IL-6 and TNF-alpha. Taken together, these data suggest that treadmill and wheel exercise protect against inflammation through the regulation of JNK/NF-kappa B signaling in experimental models of knee OA. (C) 2019 Elsevier Inc. All rights reserved.