OBJECTIVE:To explore the molecular mechanism of warming moxibustion (WM) in knee osteoarthri-tis (KOA).METHODS:The knee joints of 40 New Zealand rab-bits were placed in a plaster cast in an extended po-sition to establish a KOA model.The animals were randomly divided into four groups:the control group,model group,WM group,and diclofenac(DF) group.Hematoxylin-eosin staining and the modified Mankin score were applied to evaluate the histopathological changes.Chondrocyte apop-tosis was determined by the terminal deoxynucleo-tidyl transferase dUTP nick end labeling (TUNEL) as-say.Western blotting and real-time quantitative polymerase chain reaction were performed to mea-sure the expression of interleukin-1β (IL-1β),prosta-glandin E receptor 3 (PTGER3),a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs-5 (ADAMTS-5),matrix metalloprotein-ase-13 (MMP-13),and C-terminal telopeptides of collagen type Ⅱ (CTX-Ⅱ) in cartilage tissues of the different groups.The concentrations of IL-1β,PT-GER3,and CTX-Ⅱ in serum were detected by the enzyme-linked immunosorbent assay.RESULTS:Rabbits with KOA in the WM and DF groups showed significantly reduced cartilage ero-sion and Mankin scores,compared with the un-treated rabbits.The number of TUNEL-positive cells observed in the WM group was much fewer than that in the model group.The expression of PTGER3,MMP-13,CTX-Ⅱ,IL-1β,and ADAMTS-5 in cartilage tissues was remarkably downregulated following therapy with WM and DF.Moreover,a marked re-duction was observed in the serum levels of IL-1β,PTGER3,and CTX-Ⅱ in the WM and DF groups.CONCLUSION:WM exerts favorable therapeutic ef-fects on articular injuries of KOA by regulating the expression of inflammatory and cartilage degrada-tion-related cytokines.