Different types of calcium phosphate compounds are commercially available for medical and dental applications as bone substitute materials. Biological apatites contain several kinds of minor elements such as carbonate (CO3), magnesium (Mg), and fluoride (F) in enamel, dentin, and bone. It has been shown that F ion and F-substituted apatite promoted osteoblast proliferation and inhibited osteoclast cell activity. The purpose of this study was to investigate the in vivo rat tibia activity on F-substituted apatite (FAp). Apatites of unsintered calcium deficient apatite (CDA), and FAps, with low, medium, and high F concentrations, were implanted in rat tibia for 1 and 2 weeks. Implanted tissues were embedded in paraffin blocks, stained with hematoxylin-eosin and histomorphometrically observed. Results showed that low F concentration induced better and faster new bone formation in vivo compared to CDA. Therefore the results suggested that F as a minor element in bone rendered a suitable effect on bone formation in vivo.