A robust method for inducing bone-formation without an autograft has not been established. Currently, both platelet-rich plasma (PRP) and bone morphogenetic protein (BMP) have been widely investigated for their clinical use in such cases. However, their synergistic effect is still controversial and previously shown diversity of this effect depends on various factors such as the bone substitutes involved. In this study, we investigated the synergistic effect of PRP and BMP2 on an alloplastic substitute as potentiators to induce in vivo bone-formation. A 10 mm diameter bony defect in rabbit calvarium was reconstructed using biphasic calcium phosphate (BCP) ceramics with or without PRP, recombinant human (rh) BMP2, and their combination. At 6 and 12 weeks after implantation, rabbits were euthanized and the radiographic and histomorphometric features of bone reconstruction were analyzed. The results showed that defects filled by rhBMP2/BCP with or without PRP had high bone density at 6 and 12 weeks in radiological evaluation. However, in histomorphometric analysis, the defects filled by rhBMP2/BCP with PRP showed significant new bone formation compared with that by rhBMP2/BCP without PRP, especially at 6 weeks. We propose that the synergistic effect of PRP and rhBMP2 gives highly osteoinductive properties to alloplastic substitutes in vivo.