Objective: To investigate the pathological changes and the expression of connexin43 (Cx43) in articular cartilage of rats with type 2 diabetes mellitus (T2DM) for better understanding the pathogenesis of diabetic osteoarthritis (OA). Methods: Male Zucker diabetic fatty (ZDF) rats (n = 40) with a fasting blood glucose level above 7.8 mmol/L were served as T2DM group, and age-matched control lean Zucker rats (LZR) (n = 30) with nondiabetic were served as the control. At the end of 8th, 12th, 16th, 20th and 24th week after the T2DM model were built, an experimental subgroup and a control subgroup were executed in batches and the bilateral knee joints were obtained . Paraffin sections were made from the cartilage tissues which were cut off from the medial femoral condyles and tibial medial plateaus for Safranin O staining and immunohistochemistry experiments. The damage of cartilages and the expression of Cx43 in cartilage which were assessed by Mankin’s score and immunohistochemistry, respectively, were analyzed statistically. Results: At the end of 8-24 weeks after the T2DM model were built, the Mankin’s scores and the expression of Cx43 in the cartilages of the medial femoral condyles and tibial medial plateaus of the T2DM rats were larger than those of the control rats (all P<0.05). The Mankin’s scores and the expression of Cx43 in the cartilages of the medial femoral condyles and tibial medial plateaus tended to increase with the course of T2DM (r=0.79 and 0.85 respectively, both P<0.001). Conclusion: The expression of Cx43 in the cartilages of the knee joints of rats with T2DM tends to increase with the course of T2DM, and has a positive correlation with the damage of the cartilages, which suggest that the high expression of Cx43 in the cartilages could accelerate the occurrence and development of diabetic OA.