Sensing of nucleic acids by innate immune pathways is essential for normal immunity against viruses, and defects in this process lead to autoimmune diseases such as type 1 diabetes. Cleavage of intracellular DNA is mediated by molecules of the SET complex, and this complex can be activated by the serine protease granzyme A. Mutations in molecules in the SET complex, such as the 3’ endonuclease Trex1, result in autoimmunity in mice and man that is driven by excessive production of type 1 IFN. Type I interferons (IFN) have been implicated in initiation of islet autoimmunity and development of type 1 diabetes. While studying cytotoxic T cell-mediated b cell death in type 1 diabetes, we discovered that non-obese diabetic (NOD) mice lacking granzyme A have accelerated diabetes. Granzyme A-deficient NOD mice had more islet autoantigen-specific T cells in the thymus, pancreatic lymph node and islets when compared to wild-type NOD mice. Islet expression of the type I IFN-induced genes Isg15, Ifit1 and Oas1a peaked at 3-4 weeks of age in wild-type NOD mice, corresponding with an increase in Ifnα mRNA, and IFN-induced gene expression was ablated in islets from NOD mice lacking type 1 IFN receptors (IFNAR1-/-). Islets from granzyme A-deficient NOD mice had a 6-fold increase in islet expression of these genes between 2-6 weeks of age, suggesting excessive activation of innate immunity and type 1 IFN production. While NOD.Gzma-/- mice had accelerated diabetes, NOD.IFNAR1-/- mice developed insulitis and diabetes at a similar rate to NOD controls. Our data indicate a crucial role for granzyme A in controlling activation of innate immunity. While type 1 IFN in NOD mice is not required for diabetes development, excessive activation in a genetic background that is prone to autoimmunity, results in accelerated disease.