Objective: Mandibular defects, arising from various causes, pose significant challenges in maxillofacial reconstruction. Autogenous bone grafts (AGB) are the gold standard for repair, but the effectiveness of non-vascularized bone grafts (NVBG) in larger defects remains debated. Material and Method: This study investigates the effects of adding Platelet Rich Fibrin (PRF) to NVBG in mandibular defects exceeding 6 cm, using male sheep (Ovis aries) as a model. Twenty-eight male rams were divided into control and treatment groups, and the treatment group received NVBG mixed with PRF. Fibroblast activity and bone cavity density were assessed using Scanning Electron Microscopy with Energy Dispersive X-ray Spectroscopy (SEM-EDX) after 3 and 6 weeks. Results: PRF-treated group exhibited significantly higher fibroblast activity, particularly in the contact healing sites (58.12%) compared to the control (42.64%) (p=0.015). The PRF group also demonstrated enhanced bone cavity density and faster healing rates. Conclusion: Addition of PRF to NVBG significantly improves bone regeneration in large mandibular defects, promoting fibroblast proliferation and graft stability. These findings support the clinical use of PRF in enhancing outcomes in mandibular reconstruction surgeries. © 2025 JDMFS. Published by Faculty of Dentistry, Hasanuddin University. All rights reserved.