It has been shown that fluoride ions enhance OCP hydrolysis into Ca-deficient apatite and that fluoridation in hydroxyapatite (HA) affects osteoblast activity. The present study was designed to investigate whether fluoridated Ca-deficient apatite (F-HA) formed via OCP enhances bone regeneration. F-HA was obtained through hydrolysis of the OCP in a solution containing 2 ppm fluoride at 37 °C and pH 7.4. A standardized critical-sized defect was made in the rat calvarium, and granules of F-HA were implanted into the defect. Five rats from each group were fixed through four to twelve weeks after implantation. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) confirmed that F-HA corresponded well to apatite structure. In week four, new bone matrix was formed around F-HA. In week twelve of F-HA group, newly formed bone matrix was more abundant, whereas the implanted F-HA was unresorbed and still remained. A statistical analysis in week twelve showed that the newly formed bone in the defect with F-HA was higher than that with untreated group. The fact that new bone was directly formed on F-HA implant suggests F-HA formed via OCP could be used as a bone substitute material.