This study aimed to investigate the effect of aerobic exercise combined with glucosamine (OTL) on the apoptosis of chondrocytes of rabbit knee osteoarthritis (KOA) by affecting the expression of TRPV5.After the KOA white rabbit model was established, aerobic training and OTL treatment were performed, then the model joints were evaluated by Mankin, HE staining was used to observe the pathological changes of articular cartilage, TUNEL and immunohistochemistry were used to detect chondrocyte apoptosis. Knee chondrocytes were isolated and identified by Alcian Blue and type II collagen fiber staining. The cells were treated with iodoacetic acid (MIA) to simulate osteoarthritis in vitro, and then the effect of TRPV5 on apoptosis was detected by flow cytometry, in addition, apoptosis-related proteins and TRPV5 were detected by western blotting and qRT-PCR.Both aerobic exercise and OTL treatment could significantly reduce the Mankin score of KOA model, and could effectively inhibit chondrocyte apoptosis in the KOA model, and inhibit the expression of caspase 3 and caspase 9 in the KOA model. TRPV5 expression was significantly increased in the model, while both aerobic exercise and OTL could reverse its expression. The low-expression of TRPV5 significantly reversed the role of MIA in promoting apoptosis and apoptosis-related proteins of knee chondrocytes, while overexpressing TRPV5 promoted MIA-induced apoptosis and apoptosis-related proteins.Aerobic exercise combined with glucosamine hydrochloride capsules inhibited the apoptosis of chondrocytes in rabbit KOA by affecting the expression of TRPV5.Copyright © 2022. Published by Elsevier B.V.