To investigate the effect of preoperative mycophenolate mofetil (MMF) on allograft survival in a murine corneal transplantation model. Corneal grafting was performed from Brown Norway to Lewis rats. Groups were divided as follows: Rats that received syngeneic or allogeneic grafts without therapy served as controls. MMF treatment was either started 7 days prior to transplantation and continued for 14 postoperative days (POD) or started at the day of corneal grafting until POD 14. MMF (20 mg/kg) administered postoperatively had no significant beneficial effect on corneal graft survival when compared with controls. However, the group receiving 40 mg/kg MMF postoperatively showed a statistically significant prolonged graft survival. A 1-week preoperative administration of 20 mg/kg MMF allowed superior graft survival. Priming the immune system of corneal transplant recipients preoperatively with MMF proved to be a beneficial therapeutic regimen for prolonging corneal allograft survival in rats.