Purpose: This study aimed to evaluate the effects of leucocyte- and platelet-rich fibrin (L-PRF) on the inflammatory process, tissue repair, and expression of vascular endothelial growth factor (VEGF) on bone defects in the calvaria of rats. Materials and Methods: L-PRF was obtained from three animals submitted to cardiac puncture to prepare the membranes. Two noncritical defects with a diameter of 2 mm were created in the calvaria of 15 Wistar rats. The defects on the right side were filled with a blood clot (CTRL) and the left side with L-PRF. After 5, 15, and 30 days, the animals were euthanized and the specimens processed for histologic, histomorphometric, and immunohistochemical analyses. In order to measure the intensity of the inflammatory infiltrate and VEGF expression, scores were assigned from 0 to 3, with 0 being no expression, 1 discrete (up to 25%), 2 moderate (between 25% and 50%), and 3 intense (> 50%) expression. The area of bone neoformation at the edges of the defects was also quantified. Results: A less intense inflammatory infiltrate was observed in the defects filled with L-PRF compared with CTRL at all times analyzed (P .05). At 5 days, no bone neoformation was observed in any of the groups evaluated. After 15 and 30 days, greater bone neoformation was observed in the group treated with L-PRF compared with the CTRL group (P .05). At 15 days, 3,871.8 (1,070.15) μm² were recorded for the CTRL and 49,978.5 (14,360.7) μm² in the L-PRF. At 30 days, 62,284.5 (3,579.5) μm² were observed in the CTRL and 154,076.6 (31,464.9) μm² in the L-PRF. At all evaluated times, a lower inflammatory infiltrate was observed in the group treated with L-PRF compared with the CTRL. VEGF expression was observed in the initial phase and throughout the tissue repair process in both groups. At 5 days, there was no difference in VEGF expression between the groups. VEGF was present at the initial phase and throughout the tissue repair process in both groups. In the L-PRF group, a decrease in VEGF expression was observed at 15 and 30 days compared with the CTRL group. Conclusion: L-PRF had a positive effect on the regenerative process of bony defects, with a reduced inflammatory response and greater bone neoformation. Schlagwörter: bone regeneration, fibrin, L-PRF, platelet-derived growth factor, VEGF