Although seemingly diverse, the tissue injury at sites of diabetic complications, whether in the heart, kidneys or eyes, shares the common histopathological feature of endothelial cell loss, a consequence of both increased cell death and deficient regeneration. In medium-sized and larger arteries the loss of the protective lining contributes to the atherosclerotic process, while at sites of microvascular disease endothelial cell loss leads to capillary rarefaction and ischemia. The pathophysiology of these changes and their consequences on organ structure and function in diabetes are reviewed, and the potential for endothelial regenerative strategies to enhance repair and ameliorate the long-term complications of diabetes is explored.  (Circ J 2013; 77: 849–856)