Osteoporosis is one of the most prevalent bone diseases especially among postmenopausal women. The study was conducted on 36 female rats divided into three equal groups; i) Sham operated; ii) Ovariectomized (OVX) ; iii) Leptin treated ovariectomized. Serum receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG), urinarydeoxypyridoline/creatinine (DPY)/Cr) were measured. The mRNA expression of RANKL and OPG were examined by real time polymerase chain reaction (PCR). Leptin decreased bone turnover markers and serum RANKL while it resulted in significant increase in serum Ca and OPG. Moreover, it had a significant anti-osteoporotic effect compared to OVX rats as it markedly down-regulated expression of RANKL and up-regulated expression of OPG in proximal femur, and thus lowered the RANKL/OPG ratio. These findings suggests that the anti-osteoporotic effect of leptin was by inhibiting osteoclastogenesis via modulating the RANKL/OPG ratio and that leptin can be used as alternative therapeutic agents of osteoporosis .