Temporomandibular joint (TMJ) osteoarthritis is typically a slowly progressive asymmetric disease. Little is known regarding the natural destruction of TMJ articular tissues. The aim of the present study was to investigate morphological changes in the TMJ of STR/ort mice, known to be the model for spontaneous osteoarthritis in the knee joint, and to evaluate STR/ort mice as a suitable animal model for TMJ osteoarthritis. TMJs from 32 STR/ort mice euthanized at 30, 40, 50 or 60 weeks of age, and from 6 CBA mice euthanized at 30, 40 or 60 weeks of age were examined. Toluidine blue and tartrate-resistant acid phosphatase staining were used to assess histological changes in the articular cartilage. Morphological changes in the articular cartilage of the TMJ were evaluated using microcomputed tomography. At the age of 40-50 weeks, 17 (68%) of the 25 STR/ort mice had loss of articular cartilage on histology, with cavitation and erosion of the exposed bone and gradual changes in condylar shape. Furthermore, osteoarthritic morphological changes, and structural alterations were observed by microcomputed tomography. The STR/ort mouse strain appears to develop spontaneous osteoarthritis-like lesions in the TMJ with age, and would be a useful model to study the pathogenesis of TMJ osteoarthritis.