Purpose: The aim of this study was to evaluate whether local application of platelet-rich plasma (PRP) would induce bone regeneration in cranial defects on rabbits. Materials and Methods: Twelve female New Zealand rabbits were used for this study. Two identical 10-mm-diameter bicortical cranial defects were created in each animal. One of the defects was grafted with PRP, while the contralateral was left unfilled as a negative control. Animals were sacrificed at 2, 4, 6, and 8 weeks after surgery, and biopsy specimens were evaluated histologically and histomorphometrically under light microscopy. Analysis of variance was used for statistical analysis. Results: The histomorphometric evaluation showed more regenerated bone after local administration of PRP at 2 weeks (P > .05), 4 weeks (P .05), and 6 weeks (P > .05). At week 8, new bone formation was comparable in both groups. Conclusion: In this animal model, local application of PRP in bone defects enhances healing significantly at 4 weeks. Keywords: bone regeneration, platelet-rich plasma, rabbits