Early detection and tracking of progression of osteoarthritis (OA) is challenging. OA is characterized by degradation of articular cartilage and menisci, thickening of the subchondral bone, variable degrees of synovial inflammation and hypertrophy of the joint capsule inflammation in knee-joint. Till date, the identified causative factors contributing to OA are aging, gender, obesity, heredity and overweight. However, an increased prevalence of OA among diabetes mellitus (DM) patients have been reported which portends the diabetes as risk factor for integrity of knee joint, leading to OA. Therefore, this study explored the hypothesis that hyperglycemic microenvironment which persists in diabetes would lead to increased levels of carboxymethyl lysine (CML), an advanced glycation end product (AGE) in knee-joint, particularly in articular cartilage, meniscus and subchondral bone resulting in increased tissue degradation. Firstly, we characterized OA in streptozotocin (STZ)-induced diabetes mice. The knee-joints from healthy control and diabetic origin were isolated and the structural deformities was assessed through hematoxylin and eosin staining. Besides conventional histology, immunohistochemical (IHC) staining were conducted using type II collagen and safranin O to determine the structural component of articular cartilage while accumulation of carboxymethyl lysine (CML) and presence of inflammatory cytokines, matrix metalloproteinase 1 (MMP-1) and 13 (MMP-13) were detected by IHC-CML and IHC-MMP-1 and 13 respectively. These results were also confirmed by western blot analysis. Additionally, the expression level of chondrogenic markers (SOX9, Col II and Aggrecan) were also assessed. Results demonstrated that CML, MMP-1 and 13 levels were highly increased in diabetic group mice while SOX9, Col II and Aggrecan were significantly reduced compared to their corresponding controls which are an indicative of OA-like symptoms. Conclusively, our results provides the evidence that diabetes stimulated a catabolic response leading to OA.