Purpose: To elucidate the injury of corneal allograft endothelial cells (ECs) upon rejection and the subsequent replacement process of the cells.Methods: The corneal transplantation model in an major histocompatibility complex (MHC) class I/II disparate Dark Agouti (DA)-Lewis combination was used. The rejection kinetics was observed in 16 cases in which the corneal opacity grade was recorded after grafting and after the onset of rejection. Four normal corneas and four allografts were subjected to EC staining to investigate the EC integrity in cases of rejection. Furthermore, a series of rejected allografts were examined and the EC integrity compared at one week, three weeks, three months, and six months after the onset of rejection.Results: All corneal allografts were rejected, resulting in EC integrity loss. However, the allografts recovered transparency around 18 days after the onset of rejection with repaired endothelium by regenerative ECs. Moreover, although the whole endothelium would be fully recovered after rejection, the ratio of regenerative EC density reached only half of normal levels as long as six months after the transplant.Conclusions: Corneal allograft EC replacement represents a reparative response to transplant-related injury.