A bone defect that is not repaired with bone completely is designated a non-union defect or a critical-size defect. The biological mechanism that regulates the process of bone repair of the critical-size defect remains unknown. The present study was designed to investigate bone repair in a critical-size defect compared with that in a smaller or non-critical-size defect. Our original standardized rat calvarial bone defect model was used for the experiment. The rate of bone formation was examined with X-ray morphometry and the bone production of osteoblasts and osteocytes was assessed by molecular histology with in situ hybridization for type I collagen and osteocalcin. Formation of repaired bone ceased within 24 weeks in both critical- and non-critical-size defects i.e. regardless of completion of the defect repair. The results suggested that osteoblasts and osteocytes cease bone formation, and the differentiation of osteoblast progenitors declines in 24 weeks. Also, bone repair proceeds from the periosteum on both sides of the parietal bone but not from the surface of the bony edge around the original defect. The results could provide useful information for clinical research on bone repair.