Osteoporosis is one of the most prevalent bone diseases especially among postmenopausal women. This study was conducted on 36 female rats divided into three equal groups; i) Sham-operated, ii) Ovariectomized (OVX), iii) Leptin treated ovariectomized group. At the end of experiment, blood was collected for measurement of serum alkaline phosphate (ALP), calcium (Ca), phosphorus (P), osteocalcin, receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG). Urine was collected for measurement of urinary deoxypyridoline/creatinine (DPY/Cr). After eight weeks of treatment, administration of leptin inhibited OVX-induced weight gain with uterotrophic effect, decreased bone turnover markers (urinary DPY/Cr, serum osteocalcin and serum ALP) and serum RANKL while it resulted in significant increase in serum calcium and OPG. Moreover, it markedly decreased expression of RANKL and increased 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 RANKL/OPG ratio. Leptin had potential to be developed as alternative therapeutic agents of osteoporosis induced by postmenopause