To evaluate the repairing effects of glucosamine sulfate combined with etoricoxib on articular cartilages of patients with knee osteoarthritis (KOA). A total of 106 KOA patients were randomly divided into control (n = 40) and experimental groups (n = 66) and treated with etoricoxib alone and glucosamine sulfate plus etoricoxib, respectively. Changes in WOMAC score and clinical efficacy were observed. The synovial fluid was extracted. Bone metabolism indices, growth factors, inflammatory factors, matrix metalloproteinases (MMPs), and NO-induced apoptosis-related factors were measured by ELISA. JNK and Wnt5a mRNA levels were determined using RT-PCR. After treatment, the total WOMAC scores of both groups significantly declined (P < 0.05), being lower in experimental group. The total effective rate of experimental group was higher (P < 0.05). BGP and OPG levels rose, especially in experimental group (P < 0.05). CTX-II, COMP, and RANKL levels decreased, particularly in experimental group (P < 0.05). TGF-β, IGF-1, and FGF-2 levels increased, especially in experimental group (P < 0.05). Both groups, particularly experimental group, had decreased levels of IL-1β, IL-17, IL-18, TNF-α, MMP-3, MMP-9, and MMP-13 (P < 0.05). JNK and Wnt5a mRNA levels of both groups dropped, which were lower in experimental group (P < 0.05). NO and LPO levels reduced, being lower in experimental group. SOD level rose, especially in experimental group (P < 0.05). Glucosamine sulfate plus etoricoxib can repair the articular cartilages of KOA patients. Probably, JNK and Wnt5a are downregulated to inhibit the secretion of MMPs through lowering the levels of inflammatory factors, thereby delaying cartilage matrix degradation. NO-induced chondrocyte apoptosis may be suppressed via the SOD pathway.