INTRODUCTION:Bone defects above critical size do not heal completely by itself and thus represent major clinical challenge to reconstructive surgery. Numerous bone substitutes have already been used to promote bone regeneration. Incorporation of 31biologically active molecules to bone grafts have shown to further improve its bone forming capacity. As a potential candidate for bone regenerating biomolecules which can be used in promoting proliferation and osteogenic differentiation of mesenchymal stem cells, the hypothalamic hormone oxytocin is suggested to be promising. AIM OF THE STUDY: was to evaluate the efficacy of the hypothalamic nonapeptide oxytocin (OT) by direct delivery into local defects using β-tricalcium phosphate (β-TCP) as a carrier. MATERIALS AND METHODS: Twenty one male New Zealand white rabbits weighing 3 Kg (±250 g) were used in this study. Right and left critical size bone defects (CSD) were performed in the edentulous area of rabbit mandibles (diastema). Right side bone defects (Experimental) were filled with OT loaded β-TCP, while the left side bone defects (Control), were filled with saline loaded β-TCP. The effect of OT hormone on bone formation was assessed histologically as well as histomorphometrically after 1, 3 and 6 weeks. RESULTS: Greater amount of new bone formation was noticed in the CSDs filled with the OT loaded groups. The amount of new bone formed was significantly higher during the 3 observational intervals in the OT loaded β-TCP than when compared with the saline loaded β-TCP. CONCLUSION: OT induces new bone formation via an osteoinductive action and can be added to bone grafts following surgical and periodontal surgeries to enhance bone regenerative capacity.