Background Immune rejection is the main reason of grafts failure after corneal transplantation. This study was to determine whether interlerkin-1 receptor antagonist (IL-1ra) eye drops could prolong corneal allografts survival in high-risk corneal orthotopic allotransplantation in rat model and to study the effect of IL-1ra on the expression of CID1-positive cells in the grafts. Methods For all experiments, the Sprague-Dawley (SD) rats' corneas were transplanted into Wistar rats' eyes. High-risk transplants included those that had been sutured into Wistar recipient beds with corneal neovascularization induced by placement of three interrupted sutures in the host cornea 7 days earlier. All the animals were divided, in a masked fashion, into three treatment groups and one control group. Each treatment group received IL-1ra. eye drops of different concentrations (1 mg/ml, 3 mg/ml, or 5 mg/ml, respectively) four times a day for 30 days. The control group received 0.9% normal saline (NS) eye drops in the same way as the treatment groups. All allografts were evaluated for signs of rejection from the first day after surgery. Ten days later, corneal specimens were processed to examine the expression of CD1-positive cells and histopathological changes. Results The survival time of the transplants was 5.80 +/- 0.79, 5.89 +/- 1.05, 6.78 +/- 0.83, and 9.00 +/- 2.36 days respectively in the control or three treatment groups. Compared with the control group, 1 mg/ml IL-1ra eye drop did not prolong the survival time of the allografts (t = 0.210, P > 0.05). However, 3 mg/ml and 5 mg/ml IL-1ra eye drop did prolong the survival time of the grafts (t greater than or equal to 2.627, P < 0.05), with the latter showing more obvious effect. Immunohistochemical examinations showed a significant decrease in inflammatory cell and CD1-positive cell infiltration in IL-1ra. treated groups compared with the control group. Conclusions IL-1ra can promote corneal allograft survival in a dose-dependant manner by reducing the infiltration of CD1-positive cells in high-risk corneal transplantation.