The present study was designed to investigate the mechanism of in vivo conversion from synthetic octacalcium phosphate (OCP) into hydroxyapatite (HA) at ultrastructural level, where the implanted OCP is enhancing bone regeneration in mouse calvarial bone defect. OCP granules were implanted into the subperiosteal area of the calvaria of 7-week-old BALB/c mice for 3 weeks. Transmission electron microscopy of undecalcified frontal sections, obtained from the acrylic resin-embedded skull specimens showed that the bone crystals in newly formed bone directly bonded to the OCP particles implanted. The morphological characteristic of original plate-like OCP particles was remained unchanged even after the implantation, whereas a number of de novo nano-particles were also directly formed onto the plate-like OCP particles. Some of OCP particles were linked with other OCP particles through these nano-particles. The results suggest that the OCP-apatite conversion, involving the enhanced bone regeneration, advances via topotaxial conversion without changing the original OCP morphology, accompanied by solution-mediated de novo nano-apatite formation, in the vicinity of the implanted OCP particles.