Purpose: This study evaluated effect of Moringa Oleifera (MO) gel and Platelet-Rich Fibrin ( PRF) in treatment of bone defect. Methods:16 defects were produced in 8 rabbits and divided randomly into 2 groups; group (1) buccal bone defect treated with MO hydrogel and PRF , group (2) buccal bone defect treated with PRF . Immunological and histological examination were assessed at 14 and 28 days. Results: After 14 days, PCNA and TGF-β1 showed moderate increased expression of cells in proliferating fibroblast as well as in the organized tissue with ill-defined new bone trabeculae in group 1 while, in group 2 there was mild positive expression in the proliferating fibrous tissue that was filling the defect area and to lesser extent in the proliferating fibroblast. After 28 days, there was increased expression of both PCNA and TGF-β1 of both groups. TGF-β1 was significantly higher in group 2 than group1.Masson’s trichrome stained sections revealed that after 14 days, group( 1)showed increased amount of collagen than group-2. After 28 days, there was an increased amount of osteoid tissue in group-2 than in group-1. Conclusion: MO gel + PRF has a promising effect in increasing bone regeneration .