The immediate blood-mediated inflammatory reaction (IBMIR) will be triggered when islets come in direct contact with the recipient’s blood during islet cell transplantation, which causes the rapid loss of insulin secretion function of the islet cells. This paper addresses the problems involved in the occurrence mechanism of IBMIR, including the activation of the coagulation system and complement system, and the antibodies impact, and the roles of the inflammatory mediators and inflammatory cells infiltration as well as the glucose toxicity.