Although, diabetes is reaching pandemic proportions, the exact etiology of either type 1 (T1D) or type 2 diabetes (T2D) remains to be determined. Mounting evidence, however, suggests that islet inflammation is a likely common denominator during early development of either type of the disease. In this review, we highlight some of the inflammatory mechanisms that appear to be shared between T1D and T2D, and we explore the utility of intravital imaging in the study of islet inflammation. Intravital imaging has emerged as an indispensable tool in biomedical research and a variety of in vivo imaging approaches have been developed to study pancreatic islet physiology and pathophysiology in the native environment in health and disease. However, given the scattered distribution of the islets of Langerhans within the “sea” of the exocrine pancreas located deep within the body and the fact that the islets only constitute 1 – 2% of the total volume of pancreatic tissue, studying the pancreatic islet in situ has been challenging. Here, we focus on a new experimental approach that enables studying local islet inflammation with single cell-resolution in the relevant context of the in vivo environment non-invasively and longitudinally and, thereby improving our understanding of diabetes pathogenesis.