Antioxidant agents stimulate new bone formation during the process of repair of bone defects. This study aimed to examine the effects of systemic administration of resveratrol, an antioxidant agent, on new bone formation in a rat model of experimentally induced bone defects. The study consisted of four groups. Each group was divided into 2 subgroups on the basis of the date on which the animals were sacrificed. We formed a 5-mm bone defect in the right mandible of the animals in each group. Control group (C) received no further treatment, first experimental group (G) received a bovine bone graft, second experimental group (R) received systemic administration of resveratrol (10 mg/kg), third experimental group (GR) received systemic administration of resveratrol (10 mg/kg) with a bovine bone graft. The results of histopathological examination on the 14th and 28th day showed significant differences in the degree of ossification, fibrosis, angiogenesis, and the density of inflammatory cells between the groups (p < 0.05). Results of biochemical analysis showed significant differences in the serum levels of bone morphogenetic protein-2 (BMP-2) and tumor necrosis factor α (TNF-α) between the groups (p < 0.05). Thus, our results showed that systemic resveratrol administration with graft placement may have positive effects on bone healing in critical-sized bone defects.