In the process of bone formation, the stabilization of the matrix proteins would precede the mineralization, for which covalent crosslinking reactions might be involved. In the present experiment, we assumed that the transglutamination reaction would play one of the major roles in cross-linkage for the stabilization of the bone matrix proteins. Therefore, we have studied histopathological and immunohistochemical changes, especially focusing on differential expression of the isoenzymes of transglutaminase (TGase) in the healing stages of fracture site and the epiphyseal plate of rat fibula. The expression of TGase C is noted in the undifferentiated mesenchymal cells, osteoblasts and resting or hypertrophic chondrocytes, while TGase E in the hypertrophic or calcifying chondrocytes in the callus of the fracture site and the epiphyseal plate, suggesting that the expressions of TGase C are more dominant than that of TGase E in the process of endochondral ossification. The expression of TGase C is high in the 1-2 weeks of fracture healing. From these results, it could be suggested that the expression of TGase isoenzymes might be dependent on bone fromation and would play an important role in the fracture healing as well as in the normal ossification process.