The purpose of this study was to compare the bone regenerative effect of calcium phosphate glass according to the particle size in vivo. We prepared two different sizes, that is 400 μm and 40 μm, of calcium phosphate glass powder using the system CaO-CaF2-P2O5-MgO-ZnO. Critical-sized calvarial 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 histological as well as histomorphometrical studies. The particle size of the calcium phosphate was crucial; 400 μm particles promoted new bone formation, while 40 μm particles inhibited it because of severe inflammation.