Background: Disorders of bone healing still represent major challenges in clinical care to date. However, the bone filling materials delivery require surgical implantation at the site of fracture, which may result in local complications. Therefore administered osteogenic drugs will provide an excellent method for bone lesion healing. Aim of the study: to evaluate the systemic effect of metformin administration on bone healing at bony defect site by measuring the gene expression of osteocalcin and vitamin D receptors Materials and Methods: Twenty adult male rabbits used in this study were divided into two groups, each group contains ten rabbits. All rabbits were received the same surgical procedure under general anesthesia. After surgical exposure of rabbit's femur, two holes of 3 mm diameter by 3mm depth are prepared and left empty. Metformin administered orally to the rabbits in a dose of 50 mg/kg for 28 days . Animals were sacrificed at two times intervals according to their groups at 14th and 28th day after surgery and the femur isolated, sectioned, and bone specimens taken from the site of defect, the specimen placed in phosphate buffer saline until assessed for quantitative-PCR(QPCR). Result: showed that there is increase in the quantitative gene expression of both osteocalcin and vitamin D receptors in the metformin treated group more than the control group in both time intervals of the study. Conclusion: Metformin increase bone healing and regeneration at the bone defect sites and enhance the process of osteogenesis and osseointegration more than the control untreated rabbits.