To evaluate the validity of osteoarthritis model induced by bilateral ovariectomy in guinea pig, 32-month-old female guinea pigs were randomly divided into two groups: a sham operation group (control group) and an ovariectomized group (OVX group). The animals were killed 6 or 12 weeks after the operation and the degeneration of the knees were assessed microscopically and histologically by scanning electron microscope (SEM), transmission electron microscope (TEM) and light microscope. The serum levels of estrogen and gestone were detected by immune contest assay.The scoring of articular cartilage histopathology of tibial plateau was performed by histopathological examination. The blood serum levels of estrogen and gestone were decreased significantly in the OVX group as compared with the control group 6 or 12 weeks after the operation. Joint cartilage degeneration as detected by SEM and TEM could be found at the 6th week, but severe degenerative lesions were observed at the 12th week in the OVX group as compared with the control group (P＜0.01).The histopathological score of articular cartilage in tibial plateau in OVX group was higher than that of control group, which was coincident with the changes of estrogen and the ultrastructure (P＜0.01).The findings suggested that bilateral ovariectomy in guinea pig can induce the severe osteoarthritis that is similar to the aging-induced OA in human. Therefore, the model of the osteoarthritis by bilateral ovariectomy in guinea pig in this study is valid.