The aim of this investigation was to evaluate the potential effects of the systemically delivered combination of calcium, zinc and vit-d supplementation of the locally applied alloplastic bone graft. 28 male Wistar albino rats were used in this study. In each animal, bone defects (10 mm length (sic) 3 mm width (sic) 2 mm depth) were created in the tibias. The animals were divided into four groups. In Group 1 (Control Group) rats were fed with standard rat diet. In Group 2 (Calcium Group) rats received calcium carbonate (15 mg/kg body weight) suspended in saline. In Group 3 (Calcium/Zinc Group) rats received calcium carbonate (15 mg/kg body weight) and zinc sulfate (4 mg/kg body weight) suspended in saline. In Group 4 (Calcium/Vitamin D Group) rats received calcium carbonate (15 mg/kg body weight) and Vitamin D (500 IU/kg body weight) suspended in olive oil. Histopathological analysis of samples was performed to evaluate the process of osteoblastic activity, matrix formation, trabecular bone formation and myeloid tissue in bone defects. Total amounts of osteoblastic activity, matrix formation, trabecular bone formation and myeloid tissue in Ca Group (p= 0.002), Ca/Zinc Group (p= 0.002), and Ca/Vit.D Group (p= 0.001) were significantly higher than in Control Group. The total amounts of Ca/Vit.D Group were significantly different than Control Group and Ca Group. The results of the present study indicated that the oral calcium carbonate supplementation combination with zinc may have systemic effects on accelerating bone regeneration in alloplastic bone grafted tibial defects. Further human studies involving long-term follow up and different type of bone grafts should be conducted.