Background: Obesity induces bone related diseases as a consequence of reduced bone formation and unwarranted bone resorption. Therefore, the possible impact of adipokines on osteogenesis has been considered. Nevertheless, the osteogenic properties of omentin-1 are indistinct and contentious. The objective of the current work was to determine the regulatory effects of omentin-1 on bone turnover, along with exploring the fundamental molecular mechanisms in obese rats. Methods: The present study investigated the effects of intraperitoneal omentin-1 injection (8 μg/kg, once daily, for 14 days) in rats after feeding a high-fat diet for 10 weeks to induce obesity. Metabolic parameters and bone dry and ash weights were measured; serum calcium, phosphorus, alkaline phosphatase, and growth differentiation factor-11 (GDF-11), and femur histopathological changes were analyzed. Additionally, we investigated the effect of omentin-1 treatment on AMP protein-kinase (AMPK), mammalian target rapamycin (mTORC1) and nuclear receptor peroxisome proliferator-activated receptor-γ (PPAR-γ) expression. Results: The results revealed significant improvement in metabolic, bone biochemical parameters and histopathological changes in the omentin-1 treated group with a significant increase in area % of bone. A significant down-regulation of mTORC1 was identified through AMPK/mTORC1/PPAR-γ pathway accompanied by an increase in serum GDF-11.Conclusions: Omentin-1 can significantly promote bone health and viability via down-regulation of the AMPK/mTORC1/PPAR-γ signaling pathway and up-regulation of serum GDF-11, thus it can promote bone formation and prevent osteoporosis.