Objective To analyze the effect of a Chinese medicine Zhengqingfengtongning on the expression of aggrecanase-1 ( ADAMTs-4) and aggrecanase-2 ( ADAMTs-5) in cartilage tissue of knee joint in rabbit models of osteoarthritis, and to study the mechanism of action of Zhengqingfengtongning in treatment for osteoarthritis. Methods 32 New Zealand rabbits were randomly divided into the observation group and the model group, and 16 healthy New Zealandrabbits were chosen as the blank group. The blank group did not receive the intervention treatment, the model group received physiological saline in gastric gavage, the observation group was given the Zhengqingfengtongning by gastric gavage. The soft tissue samples of knee joint in the three groups were taken at 4 weeks after drug intervention. The joint morphology, joint fluid and articular cartilage were observed by histopathology. The ADAMTs-4 and ADAMTs-5 mRNA were detected by RT-PCR. The data were then statistically analyzed. Results The grades of articular cartilage and Mankin’s score of the model group were significantly higher than those of the observation group and blank group, the grades of articular cartilage and Mankin’s score of the observation group were significantly higher than those of the blank group, and the difference between the two groups was statistically significant ( P < 0.05). The ADAMTs-4 and ADAMTs-5 mRNA expressions of the model group were significantly higher than those of the observation group and blank group. The ADAMTs-4 and ADAMTs-5 mRNA expressions of the observation group were significantly higher than those of the blank group, and the difference between the two groups was statistically significant ( P < 0.05). Conclusions The Zhengqingfengtongning can improve the degree of joint lesions in osteoarthritis animal models, which may be related to inhibiting the expression of ADAMTs-4 and ADAMTs-5.