For the success of xenotransplantation, hyperacute rejection must be controlled. Hyperacute rejection is induced by the activation of complement system via alternative pathway and/or classical pathway. Complement regulatory factors can inhibit activation of complement system via the both pathways. To overcome hyperacute rejection in organ xenotransplantation, gene engineering in the establishment of xeno-endothelial cells and transgenic animals (mouse and pig) using human complement regulatory factors are studied. In the near future, transgenic pig using human complement regulatory factor genes can be used as a potential donor in organ xenotransplantation.