*Purpose: Islet transplantation is a useful treatment option for insulin dependent diabetes mellitus with severe hypoglycemic event. However, intraportal islet transplantation is known to induce IBMIR immediate after islets encountering recipient blood in portal vein. IBMIR is featured by drastic activation of innate immune system, which is complicatedly associated with complement system and coagulation system. Cytokine storm, which is a main component of IBMIR, immediate after transplantation destroys transplanted islets and the outcome of the metabolic function can get worse. IL-1β is known as a key factor to induce activation of innate immune system in intraportal islet transplantation. NLRP3 inflammasome which is a protein complex existing in cytoplasm activates cytoplasmic IL-1β through caspase 1, which is a component of NLRP3 inflammasome, reacting proIL-1β. In this study, we aimed to demonstrate the effect of NLRP3 inhibitor in intraportal islet transplantation in rodent model.

*Methods: C57BL/6J male mice were used as donor and recipient for syngeneic transplantation to demonstrate activation of innate immune system. Blood glucose level was measured during one month. To clarify the mechanism of improvement of transplant outcome, culturing islets were examined by qPCR and counting islets. and also histological staining was performed in liver samples early after transplantation.

*Results: In the transplant experiment, glucose fluctuation was reduced in treatment group of NLRP3 inhibitor to recipient mice. In culturing assay of islets exposed cytokine, NLRP3 inhibition reduced up-regulation of IL-1β and survival ratio of islets through culturing period was improved in treatment group. Histological staining of TUNEL revealed reducing the number of apoptotic cells in transplanted islets at early after intraportal islet transplantation. Moreover, islet transplantation induced infiltration of inflammatory cells around islets and NLRP3 inhibitor suppress the infiltrated inflammatory cells.

*Conclusions: In this study, it was concluded that NLRP3 inhibitor can improve glycemic control after islet transplantation by reducing apoptosis of infused islets and infiltration of inflammatory cells.

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