High-risk corneal transplantation immunological rejection is a primary factor affecting the success or failure of the corneal transplantation. As a result, application of immunosuppressive agent in high-risk corneal transplantation rejection reaction occupies an irreplaceable position. However, many local and systemic adverse reactions appeared in the process of application. In order to improve the achievement ratio of the corneal transplantation, experts and scholars at home and abroad have obtained remarkable achievements in dosage form, route of administration and drug combination; meanwhile, a considerable progress was also made in genetic engineering. This paper is a review of prevention and treatment on high-risk corneal graft rejection reaction.