Abstract: Objective To observe the roles of subconjunctival administration of interleukin-1 receptor antagonist (IL-1ra) promoting corneal graft survival in rat models of high-risk penetrating keratoplasty. Methods Corneal vascularization was induced in 40 Sprague-Dawley rats (40 eyes) by passing 10-0 silk suture through the corneal stroma, and 30 of these rats received corneal grafts from Wistar rats to establish high-risk keratoplasty models and were divided into 3 groups to receive their respective treatment with IL-1ra eye drops (50 μg/ml), 1% CsA eye drops, administered 3 times a day, or no treatment. All the rats were treated by Tobra Dex eye drops and Tropicamid eye drops, 3 times a day for 14 consecutive days after the operation. During the 30-day observation, the survival of the grafts was recorded, and all the grafts were evaluated for signs of rejection. Results The mean survival times (MST) of the grafts of the treatment groups with IL-1ra and CsA were 12.00±1.50 d and 10.44±1.13 d respectively, significantly longer than that in the untreated model group (8.00±1.25 d, t=0.00, P<0.01), and the difference in the MST between the 2 treatment groups was also significant (t=0.00, P<0.01). Conclusion Treatment with IL-1ra may significantly prolong high-risk corneal allograft survival.