Background: Osteoporosis is mostly common in postmenopausal women due to estrogen deficiency and also seen as an early complication in type 1 diabetes mellitus. Moreover, C-peptide is the active secretory component of B-cells of the pancreas and is known to possess beneficial effects in diabetic complications and may have a role in the conditions of low bone mineral density. Objective: To evaluate the potential protective effects of C peptide in bone metabolism on ovariectomy-induced bone loss in non-diabetic rats. Materials and methods: 32 adult female albino rats were ovariectomized then, treated in presence or absence of Cpeрtide in a dose 75пg/kg injected subcutaneously twice daily for 8 weeks. Serum glucose, insulin, phosphate, calcium, Serum Alkaline Phosphatase, Serum Estradiol and Serum C-peptide were measured. Bone concentrations of calcium, phosphorus and femoral bone ash weights were measured. Histopathological changes in the bone were evaluated by Hematoxyln and Eosin. Results: Ovariectomy significantly increased the mean values of serum levels of C peptide, insulin, glucose, HOMAIR and alkaline phosphatase, but the mean values of serum level of estradiol, bone concentrations of calcium, phosphorus and femoral bone ash weights were significantly low. The bone concentrations of phosphorus and calcium were significantly improved by C-peptide treatment in ovariectomized rats. Conclusion: C-peptide has a potential bone protective effect against ovariectomy-induced bone loss. This can be attributed to its ability to activate Cat+-dependent signaling pathways. Key words: ovariectomized, C-peptide, Bone-Protective.