Background: Osteoporosis is a serious worldwide skeletal illness manifested by diminished bone density with increased susceptibility to fractures and increases with aging. Kisspeptin is a hypothalamic neuropeptide that regulates the gonadal hormones and was suggested to have a positive effect on bone metabolism. Material & Methods: 30 male rats were divided equally in to three groups: Sham, orcidectomized (ORX), and kisspeptin-10 (kiss)-treated groups. Blood, urine, and femoral bone samples were taken for biochemical, histopathological, and gene studies. Results: ORX rats showed increased serum levels of alkaline phosphatase (ALP), osteocalcin, RANKL, RANKL/ Osteoprotegerin (OPG) ratio, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6(, while decreased serum OPG level and bone minerals associated with disruption of bone architecture compared with Sham group. Chronic treatment with kisspeptin-10 significantly enhanced bone architecture, increased bone minerals, improved RANKL/OPG ratio, up-regulated mRNA expression levels of OPG, bone morphogenic protein 2 (BMP-2), Wnt3a, and β-catenin as compared to untreated ORX rats. Conclusion: Chronic treatment with kisspeptin-10 enhances osteogenesis and reduces bone resorption in ORX rats via modulating RANKL/OPG ratio, BMP-2, and Wnt/β-catenin signaling pathways. So, the present study recommends kisspeptin-10 as a promising novel therapeutic agent for age-related osteoporosis in men.