INTRODUCTION: This study investigated the effect of periosteal graft + platelet-rich plasma (PRP) combination on facial bone defect healing. METHODS: Five-millimeter critical sized defects in zygomatic arches of 12 adult New Zealand rabbits were created. Rabbits were randomly divided into 3 groups: First group (control group): bone defects of left zygomatic arches of 6 rabbits were wrapped with a silicone tube. Second group (periosteal graft group): bone defects of left zygomatic arches of 6 rabbits were wrapped with periosteal graft. Third group (experimental group): bone defects of right zygomatic arches of 12 rabbits were wrapped with periosteal graft-PRP combination. New bone formation was evaluated at 8th and 16th weeks. One rabbit was sacrificed at 8th week. Remaining 11 rabbits were imaged with 3-dimensional computed tomography (CT) at 16th week; then, zygomatic arches were removed for micro-CT and histologic examinations. RESULTS: Three-dimensional CT analysis at 16th week revealed no significant difference between groups regarding new bone formation (P = 0.232). Micro-CT analysis of new regenerated bone at 16th week displayed significant differences between groups 1 and 3 regarding mean bone volume (BV, mm) (P = 0.028) and mean bone mineral density (BMD, mm) (P = 0.001). There was no difference between groups 2 and 3 or between groups 1 and 2, regarding BV or BMD. Histological Bone Regeneration Scorings at 16th week displayed significant difference between groups (P = 0.015). Negative correlation between 3-dimensional CT and histologic results (r = 0.120); positive correlations between BV/BMD values in micro-CT and histologic results (r = 0.524 and r = 0.456) were found. CONCLUSIONS: By enhancing bone formation capacity of periosteal grafts, periosteal graft-PRP combination provided bone formation having more volume and density comparing with silicone tube application.