Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) have been revealed in the pathogenesis of primary osteoporosis and other metabolic bone diseases. This study was designed to assess the effect of 17-β estradiol (E2) treatment and angiotensin converting enzyme inhibitor (ACEI), captopril, on osteoporosis induced by ovariectomy in rats and discussing the role of OPG/RANKL ratio in their action. Thirty two adult female rats were divided into four equal groups. Group I: control group, Group II: ovariectomized (OVX) non treated group, Group III: OVX rats treated with E2, Group IV: OVX rats treated with captopril. OVX rats showed a significant decrease in serum Ca2+ and OPG levels with significant increase in serum RANKL, osteocalcin, alkaline phosphatase activity and urinary hydroxyproline levels. Treatment with captopril as well as E2 led to a significant improvement in bone markers levels with a significant increase in OPG/RANKL ratio. Image analysis technique revealed that there was a significant improvement in cortical bone thickness (CBT) and mean trabecular bone density (TBD) in OVX rats treated with either E2 or ACEI. So, we can conclude that the protective effect of E2 and ACEI on osteoporosis may be mediated by influencing OPG/RANKL signaling.