Type 1 diabetes is caused by T-cell-mediated destruction of the insulin-producing beta cells in the pancreatic islets. Cytokines, including interferons, interleukin-1 (IL-1) and tumor necrosis factor (TNF) play important roles in the autoimmune T cell responses against beta cells in humans and mouse models. There are three types of interferons: type I (IFNα/β), type II (IFNγ) and type III (IFNλ). IFNγ promotes beta cell-T cell interaction by upregulating MHC class I on beta cells, and mice lacking IFNγ responses are resistant to CD8+ T cell-dependent diabetes. Type I IFN stimulates a transcriptional signature in the islets, suggesting that it is essential in the triggering of autoimmunity. Mice lacking TNFR1 did not develop diabetes, and mice lacking IL-1R had delayed onset of diabetes. In both cases the number or suppressive function of CD4⁺CD25⁺FoxP3⁺ T regulatory cells was improved, indicating that TNF and IL-1 are involved in regulation of the anti-beta cell immune response. Although inflammatory cytokines are able to kill beta cells in vitro, when we transplanted islets from non-obese diabetic (NOD) mice lacking receptors for inflammatory cytokines (IL-1R, TNFR1 or IFNγR2), into wild-type NOD mice they were killed, indicating that cytokine action on beta cells is unlikely to be required for killing. Overall our data suggest that blocking inflammatory cytokines may not directly prevent beta cell killing, but may reduce recognition of beta cells, prevent triggering of disease, or increase the regulatory function of the immune system in autoimmune diabetes. Inhibitors of cytokine signalling are approved for clinical use for other diseases. Thus we have powerful tools for manipulating cytokine responses in patients with type 1 diabetes.