Toll-like receptors (TLRs) are receptors of the innate immune system specialized in recognizing conserved molecular pattern of pathogens and initiating an appropriate immune response. Along with the recognition of foreign materials, TLRs have also been shown to respond to endogenous molecules, thus mediating the development of autoimmune diseases. Type 1 diabetes (T1D) is a prototypic autoimmune disease in which TLRs play a pathogenic role. We here describe a protocol to study the role of TLRs in the development and progression of T1D by resorting to the nonobese diabetic (NOD) mouse model.