Allograft rejection is still a main cause of graft failure in high-risk keratoplasty. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis of tumor cells without significant toxicity and inhibit autoimmune disease. Therefore, we attempted to determine the roles of TRAIL in graft survival.Thirty-two BALB/C mice were recipients of corneal grafts from C57BL/6 mice. The 32 eyes were equally divided into four groups receiving graft without incubation with viral preparations, graft immersed in Dulbecco's minimum essential medium containing soluble human death receptor 5 (sDR5) before transplantation, graft carrying the recombinant adenovirus with TRAIL gene (Ad-TRAIL), and graft carrying the recombinant adenovirus with green fluorescent protein (Ad-GFP), respectively. Pathologic and immunohistochemical examinations were performed, and apoptotic cells were detected.High levels of TRAIL expression were detected in the Ad-TRAIL group, which lasted more than 2 weeks. The mean graft survival time was 17.7, 12.3, 22.0, and 17.4 days for control group, sDR5 group, Ad-TRAIL group, and Ad-GFP group, respectively. The degrees of inflammation in tissue sections taken from all groups after the onset of rejection were similar. There were more apoptotic cells in the graft of the Ad-TRAIL group than in other groups.TRAIL appears to play an important role in corneal-allograft rejection and may be used to prolong the survival of allografts.