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Diabetic hyperglycemia has been suggested to play a role in osteoarthritis. Peroxisome proliferator‐activated receptor‐γ (PPARγ) was implicated in several pathological conditions including diabetes and inflammation. The detailed effects and mechanisms of hyperglycemia on cartilage damage still need to be clarified. Here, we investigated the role of PPARγ in hyperglycemia‐triggered chondrocyte/cartilage damages using a human chondrocyte culture model and a diabetic mouse model. Human chondrocytes were cultured and treated with high concentration of glucose (30 mM) to mimic hyperglycemia in the presence or absence of pioglitazone, a PPARγ agonist. Streptozotocin (STZ) was used to induce mouse diabetes. Our data showed that high glucose induced the protein expressions of cyclooxygenase‐2 (COX‐2) and production of prostaglandin‐E₂ (PGE₂), interleukin‐6 (IL‐6), and metalloproteinase‐13 …