Abstract: Xenotransplantation is a potential solution to the shortage of human organs. In the previous 100 years, xenotransplantation has witnessed preliminary attempts and persistent progress. At present, it has entered a new stage of rapid development and achieved a series of results. Nevertheless, the management of xenotransplantation rejection is more challenging compared with that of allogeneic organ transplantation rejection. Therefore, researchers have developed a series of immunosuppressive strategies, such as use of genetically modified pig donors, use of traditional and novel immunosuppressants, and co-transplantation of donor pig thymus with donor organs, aiming to adjust the immune system response of recipients, mitigate the intensity of rejection and prolong the survival time of grafts. In this article, research progress in the mechanism, prevention and treatment strategies of xenotransplantation rejection was reviewed, aiming to provide reference for accelerating subsequent development of xenotransplantation.