A single intra-articular injection with bacterial collagenase in the right knee joints of 10-week-old male C57bl10 mice led to osteoarthritic lesions within a few weeks in these joints. The collagenase-induced osteoarthritis was characterized by severe degenerative cartilage lesions on the medial side of the femorotibial joint associated with patellar dislocation to the medial side of the joint, sclerosis of subchondral bone below the cartilage erosions, osteophyte formation, and consequent deformity of the knee joints. The osteoarthritic alterations in the collagenase model closely resembled the changes observed in spontaneous osteoarthritis in aged mice. The intra-articular injection with collagenase probably results in damage to collagen type I-containing joint structures, such as tendons, ligaments and menisci, leading to an instable knee joint that results in the osteoarthritic joint lesions observed in this model. The collagenase-induced osteoarthritis model offers the possibility of studying experimental osteoarthritis in large animal groups of inbred strains within a restricted time span at low costs.