Background: Osteoarthritis (OA) is the most common age-related joint degenerative disease, which is associated with post menopausal females.  Aim of Work: To compare the effect of hormonal replacement therapy (HRT) (Oestrogen and Progesterone) versus calcitonin administration on articular cartilage of the knee joints in murine model of osteoarthritis induced by ovariectomy.  Materials and Methods: Thirty six adult female rats were divided into five groups. Group I: control; Group II: sham operated; Group III: ovariectomized rats: Group IV: ovariectomized then received HRT )1ml/kg(0.2ml)/day IM ((for 8 weeks); GroupV: ovariectomized then received calcitonin )2 IU/kg/day (0.04ml) SC( (for 8 weeks). The rats of each group were sacrificed after 8 weeks. Articular cartilage of knee joints were processed and stained with Haematoxylin and Eosin, Alcian blue, PAS, immunohistochemical staining of Bcl-2 and statistical analysis were applied.  Results: Ovariectomy resulted in degeneration, apoptosis and deterioration of normal structure of articular cartilage, with decreased PAS reaction, decreased Alcian blue staining, and weak immunoreactivity for Bcl-2 when compared with the control and sham operated groups. Calcitonin and HRT supplementation after ovariectomy mostly prevented these changes.  Conclusion: It could be concluded that OVX causes severe changes in articular cartilage and these changes are more evident with time. HRT had a significant effect in prevention of cartilage degradation in OVX model of OA. Calcitonin administration greatly improves the histological architecture of the articular cartilage. So calcitonin had a significant effect in prevention of cartilage degradation in OVX model of OA. It can be considered as a potential therapeutic agent in OA.