The nonobese diabetic (NOD) mouse is the most useful model of autoimmune type I diabetic. NOD mice spontaneously develop marked infiltration of T cells into the pancreatic islets. The infiltrating T cells selectively destroy the pancreatic β cells. In addition to diabetes, NOD mice spontaneously develop autoimmune responses involving other tissues, including salivary gland, lacrimal gland, thyroid gland, parathyroid gland, adrenal gland, testis, large bowel, and red blood cells. NOD mice also are susceptible to exogenously induced autoimmune thyroiditis, colitis-like wasting disease, encephalomyelitis and SLE. Defects related to severalngenes, including the MHC class II, CTLA-4 and IL-2, have been associated with the susceptibility to diabetes. T cells play an important role in the development and progression of disease, whereas B cells are not required at the effector stage of type I diabetes in NOD mice.