We evaluated the role of preoperative versus postoperative systemic Cyclosporin A (CsA) on corneal allograft survival in the rat model. All treatment regimens were administered by daily intramuscular injection until rejection. In the preoperative group (n = 9), CsA (7.5 mg/kg/day) was started ten days preoperatively. In the postoperative group (n = 9), CsA (7.5 mg/kg/day) was started immediately postoperatively. In the injectable control group (n = 7), injections of 0.9% normal saline with olive oil began the day of surgery. A masked observer performed alternate day slit lamp evaluations of graft opacity, edema, and vascularity. The median rejection times [days (range)] for the injection control, preoperative and postoperative groups were: 11 (10-17), 17 (12-53), and 28 (12-53), respectively. The grafts in the postoperative and preoperative treatment groups survived longer than the control (p = 0.003 and p = 0.005 respectively). There was no statistical difference between the preoperative and postoperative groups (p = 0.3). Preoperative systemic administration of CsA may offer no significant benefit in prolonging allograft survival over treatment beginning the day of surgery.