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BACKGROUND: Papain inducing knee osteoarthritis has no direct effect on collagen and chondrocyte compared with other chemical inducers. OBJECTIVE: To evaluate the effectiveness of early osteoarthritis model of knee joint in rats by the surface morphology, radiology and histopathology of cartilage. METHODS: Twenty adult male Wistar rats were provided by Qinglongshan Animal Breeding Farm of Jiangning District, Nanjing, and the study was approved by the Ethics Committee of Liuhe Hospital Affiliated to Yangzhou University Medical College. The rats were randomly divided into control and experimental groups. At 1, 4 and 7 days, 4% normal saline and 4% papain were injected into the rat right knee joint cavity in the control and experimental groups, respectively. Rats were killed at 10 days. The articular cartilage morphology,X-ray and three-dimensional CT images were observed before the execution. Histopathological examination was performed immediately after the execution, and the results were verified by Mankins and OARSI scores. RESULTS AND CONCLUSION: (1) Compared with the control group, in the experimental group, the limp was obvious, the knee joint swelling on the injection side was obvious, and the hind limbs were unwilling to land. Radiological examination showed that the joint space narrowed obviously, and the value of three-dimensional CT joint space was significantly decreased [(0.680 0±0.016 3)vs.(0.558 0±0.033 9) mm, P < 0.05]. (2) Microscopic examination showed early stage inflammation characteristics at the right knee joint in the experimental group. There were significant differences in the Mankins and OARSI scores (P < 0.05). (3) In summary, early knee osteoarthritis induced by intra-articular injection of papain into the right knee joint of rats can be used in relevant clinical studies, because it provides measurable changes in joint motion, tactile abnormal pain, progressive radiodegeneration and micro-inflammation of articular cartilage, representing the evaluation of osteoarthritis, and providing a basis for studying the pathogenesis of early knee osteoarthritis. [ABSTRACT FROM AUTHOR]