Fulminant type 1 diabetes is defined as a subtype of type 1 diabetes with a remarkably acute onset. A nationwide survey identified that this variant accounts for approximately 20% of acute-onset type 1 diabetic patients in Japan. Recent studies indicate that this is not a minor subtype in other East Asian countries. As genetic factors, we revealed association of HLA-DR-DQ, HLA-B and CTLA-4 to fulminant type 1 diabetes. As an environmental factor, viral infection would contribute to the development of this subtype. Cellular infiltration to islets was detected soon after the onset but not observed 1 month after the onset. Macrophages and T cells were the main components of the infiltrates. Enterovirus RNA and Toll-like receptor-3 expression, a signature of viral infection, was also observed. These findings suggest that viral infection in the susceptible individual might trigger anti-viral immune response and that pancreatic beta cells are rapidly destroyed through the accelerated immune reaction.