To evaluate the effect of different concentrations 0.03%, 0.1% and 0.3% of FK 506 on xenograft corneal rejection, guinea pig corneas were transplanted into rats. FK 506 was then applied topically four times a day for 21 days. The grafts were inspected and scored according to opacity, edema, and graft protrusion. All grafts in the control group were rejected by the 14th postoperative day, and grafts in the FK 506 treated groups began to be rejected by the 17th postoperative day. Inflammatory cell infiltration was less dense in the FK 506 treated grafts than in the control group. Higher concentrations of FK 506 appeared to be more effective in preventing and decreasing the severity of the graft rejection. Topical FK 506 can delay the development of xenograft corneal rejection and decrease its severity in this animal model.