Background and objectives: Guided bone regeneration is a term used to define the use of barri-er membranes to promote complete osteogenesis. The aim of study was to histologically com-pare the effect of platelet rich fibrin membrane and resorbable Collagen membrane on bone substitute healing. Methods: in this experimental study three sheep’s which their weighted between 60-70 kg were used. After intramuscular sedation and local anesthesia, eighteen defects were created about 8 mm in diameter and 5 mm in depth in the lower border of mandible. Six defects on each animal which three in right side and three in left side of the mandible. The defects were filled with Biphasic calcium phosphate bone substitute. The first defect was covered by platelet rich fibrin membrane, the second one covered by Collagen membrane, and third one was left uncovered. The animals were sacrificed at 2, 6, and 12 weeks. Results: The healing of the grafted defects was histologically studied in all groups, and there was non-significant difference between PRF membrane and collagen membrane in healing of bone substitute at 2, 6, and 12 weeks.There was significant deference between PRF membrane and collagen membrane at 6 weekregarding scaffold replacement with mature bone. Conclusion: The use of PRF membrane shows a good outcome as a low cost biological material capable of improving bone healing defects, grafted with bone substitute. Keywords: Platelet rich fibrin membrane, collagen membrane, bone graft, bone healing.