The purpose of this study was to investigate the bone regenerative effect of calcium phosphate glass in vivo. We prepared two different sizes of calcium phosphate glass powder using the system CaO-CaF2-P2O5-MgO-ZnO; the particle size of the powders were 400 microm and 40 microm. 8 mm calvarial critical-sized defects were created in 60 male Sprague-Dawley rats. The animals were divided into 3 groups of 20 animals each. Each defect was filled with a constant weight of 0.5 g calcium phosphate glass powder mixed with saline. As controls, the defect was left empty. The rats were sacrificed 2 or 8 weeks after postsurgery, and the results were evaluated using radiodensitometric and histological studies; they were also examined histomorphometrically. When the bigger powders with 400 microm particle were grafted, the defects were nearly completely filled with new-formed bone in a clean healing condition after 8 week. When smaller powders with 40 microm particle were transplanted, new bone formation was even lower than the control group due to a lot of inflammatory cell infiltration. It was concluded that the prepared calcium phosphate glass enhanced the new bone formation in the calvarial defect of Sprague-Dawley rats and it is expected to be a good potential materials for hard tissue regeneration. The particle size of the calcium phosphate was crucial; 400 microm particles promoted new bone formation, while 40 microm particles inhibited it because of severe inflammation.