Background: (BMP)-2 has a crucial role in the treatment of extensive bone defect. However, data about the optimal dosage of (BMP)-2 in the massive bone defect casesis rare. Methods: Twenty-five SD rats were randomly allocated into a control group of hydroxyapatite (HA) alone (Group I), HA+(BMP)-2 1μ g/mL (Group II), HA+(BMP)-2 5 ug/mL (Group III), HA+(BMP)-2 10 μ g/mL (Group IV), and HA+(BMP)-2 20 ug/mL (Group V). Osteotomies were performed in each group with 10 mm bone defect in the right femur, followed by fixation and filling the defect. The fracture healing was evaluated by histomorphometry, and radiographs using RUST score. Results: We found there were significant differences in the mean total area of callus between the treatment groups (P<0. 001); there were significant differences in the mean area of woven bone between group II, III, IV, and V with the control group (respectively P=0. 009, P=0. 016, P=0. 009 and P=0. 016), the area of the cartilage between the treatment groups and control group (respectively P=0. 009, P=0. 009, P=0. 009 and P=0. 028). A statistically significant difference was found in the average area of fibrosis between group II and control group, group IV and control group (respectively P=0. 047 and P=0. 009). RUST scores showed significant differences between the control group and group II, III, IV, V (respectively P=0. 005, P=0. 006, P=0. 005 and P=0. 006). Conclusion: The administration of (BMP)-2 stimulates the formation of bone bridging in a massive bone defect. The bone bridging filling massive bone defect depends on the dose or concentration of (BMP)-2. Administration of an optimal dose (10 μ g/mL) of (BMP)-2 demonstrates better result than lower or higher dose for massive bone defect healing in SD rate.