Age-related macular degeneration(AMD)is the leading cause of blindness among the elderly worldwide. AMD is classified as either neovascular(wet)or non-neovascular(dry). The dysfunction and loss of retinal pigment epithelial(RPE)cells is regarded as the main pathological changes of AMD. The recent development of regenerative medicine has witnessed RPE cell-replacement therapy as a new approach to treat AMD, resulting in obvious visual improvement in various studies. However, there are still many problems and challenges that remain unsolved, including graft rejection. This review introduces subretinal immune environment under both normal and AMD condition, putting emphasis on immune response to allogeneic RPE. Lastly, strategies to prevent graft rejection are discussed.