Type 1 diabetes (T1D) results from a complex interplay between varying degrees of genetic susceptibility and environmental factors which have been implicated in the pathogenesis of disease both as triggers and potentiators of beta cell destruction. Activated T cells, and more specifically CD8 T cells, are the main cell type implicated in the pathogenesis of the disease and when exposed chronically to low doses of antigen, are significantly skewed toward a proinflammatory phenotype. Here we report that CD8 T cells are abundant in the exocrine pancreas of diabetic subjects, and not only in the endocrine areas. Autoantibody positive, T1D and T2D subjects present significantly higher CD8 T cell density in the pancreas without the presence of prominent insulitis, indicating that there is spontaneous infiltration of the exocrine pancreas and not only of the islets. CD8 T cells are present in the exocrine pancreas in large numbers even in diabetic subjects without remaining insulin containing islets (ICIs), which indicates a possible major role of the exocrine pancreas in the initiation/development of disease. Our study provides the first information on the precise tissue distribution of CD8 T cells in healthy, pre-diabetic and diabetic subjects and could point towards a hence unknown cause for this disease that is not exclusively autoimmune in nature.