© 2019, Sociedade Brasileira para o Desenvolvimento de Pesquisa em Cirurgia. All rights reserved.Purpose: To investigate the effects of allopurinol administration on osteoinductive reaction and bone development with graft material. Methods: Thirty-six Wistar albino rats were divided into 3 groups. In the control group, calvarial bone defect was only created without any treatment. In the Defect + Graft group, allograft treatment was performed by forming 8 mm calvarial bone defect. In the Defect + Graft + Allopurinol group, alloplastic bone graft was placed in the calvarial bone defect and then, allopurinol (50 mg/kg/day) treatment was intraperitoneally applied for 28 days. Results: Histopathological examination revealed inflammation, congestion in the vessels, and an increase in osteoclast cells in the defect area. We also observed that new osteocyte cells, increase in connective tissue fibers, and new bone trabeculae. Osteopontin expression was positive in osteoblast cells and lacunated osteocyte cells were located in the periphery of the new bone trabeculae. Osteopontin expression was also positive in osteoblasts and osteocytes cells of new bone trabeculae in the graft site. Conclusion: It has been shown that allopurinol treatment in rat calvaria defects may induce osteoblastic activity, matrix development, mature bone cell formation and new bone formation when used with autogenous grafts.