The progression of type 2 diabetes is mediated to a large extent by the deaths of β-cells, the cells in the pancreas that synthesize and secrete insulin. We discovered that ARC (Apoptosis Repressor with CARD), an endogenous inhibitor of cell death, is expressed at high levels in β-cells of the mouse pancreas. Using cell culture studies and genetic mouse models, we have further demonstrated that ARC functions as a critical β-cell survival factor during type 2 diabetes. However, little is known about the expression patterns of ARC in human β-cells and other cells within the endocrine pancreas. This information is critical for understanding the role of ARC in the pathogenesis of diabetes in humans. We have assessed whether ARC levels in islets decrease during diabetes, and found no significant changes in ARC abundance in old versus young ob/ob mice. Unexpectedly, however, we observed that the subcellular localization of ARC differs in diabetic versus non-diabetic mice. In this study, we propose to characterize ARC expression in islet cells of human pancreatic tissue from non-diabetic individuals and those with type 2 diabetes.