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OBJECTIVE To investigate the effects of different running intensities on interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in patients with early knee osteoarthritis (KOA). STUDY DESIGN Clinical comparative study. PLACE AND DURATION OF STUDY Department of Orthopedics, Longyan First Affiliated Hospital of Fujian Medical University, Fujian, China, from January 2019 to January 2021. METHODOLOGY A total of 131 patients with early KOA admitted to Longyan First Hospital Affiliated to Fujian Medical University from January 2019 to January 2021 were selected and randomly divided into four groups using the random number table method: Group A (static control group, 34 cases), Group B (walking group, 32 cases), Group C (brisk walking group, 32 cases), and Group D (jogging group, 33 cases), and the training duration of the four groups was 6 months. Moreover, the levels of IL-6 and TNF-α, the activity of daily living (ADL), Fugl-Meyer assessment scale (FMA) scores, and adverse events before and after training were compared between the four groups. RESULTS No statistical significance was observed in the differences of TNF-α, IL-6, ADL-advanced ability, ADL-basic ability, FMA-upper limb, and FMA-lower limb among the four groups before training (p>0.05). After training, the levels of TNF-α and IL-6 of the four groups were decreased, while the scores of FMA and ADL were increased. Group C had the highest FMA-upper limb and FMA-lower limb scores, ADL- advanced ability and ADL-basic ability after training, which were higher than those in groups A, B, and D (p<0.05). No statistical significance could be observed in the difference in the adverse event rate among the four groups during training (X2=3.339, p>0.05). CONCLUSION Exercise training of different intensities, such as slow walking, brisk walking, and jogging, is touted to enhance the overall recovery of patients with early KOA. The exercise intensity of brisk walking training is moderate, and the activity of daily living and exercise ability of patients are significantly improved after training, while the levels of TNF-α and IL-6 are obviously decreased. KEY WORDS Knee osteoarthritis, Interleukin-6, Exercise training, Exercise intensity, Tumor necrosis factor α.