Diabetes is marked by degenerative pathology in blood vessels. The macro and microvascular complications arising from diabetes impose an ever-increasing burden on healthcare authorities globally. The precise molecular defects that lead to diabetes-related vascular cell dysfunction, and endothelial cells in particular, remains ill-defined. This lack of understanding has seriously limited therapeutic options for conditions such as retinopathy, neuropathy, nephropathy and accelerated atherosclerosis in patients with diabetes. There is a pressing requirement to identify definitive pathways that initiate cell damage and drive progression to overt micro and macrovasculopathy. This presentation will review the molecular pathogenesis of diabetic microvascular complications, with particular emphasis on restoring function to the endothelium, especially in the context of diabetic retinopathy (DR). Patients with DR may irreversibly lose sight as a result of the development of diabetic macular oedema (DMO) and/or proliferative diabetic retinopathy (PDR). Endothelial dysfunction and degeneration plays an essential role in their pathogenesis. For example, with prolonged exposure to the diabetic milieu the replicative potential of the endothelium can become exhausted leading to a premature senescent phenotype. It has been proposed that the primary defect in DR (and other microvasculopathies) lies with the vascular endothelium and that these complications could be considered to be, at least in part, “endotheliopathies”. Indeed, damage to these cells impacts on the normal function of other cells in the capillary complex. The precise basis of endothelial, dysfunction in the diabetic microvasculature in vivo remains obscure but is most likely related to an array of cumulative biochemical insults coupled with impaired ability of the cells to repair and renew themselves. Our group has focused on the reparative potential of endothelial progenitor cells (EPCs). EPCs are a low-frequency population of circulating cells known to be recruited to sites of vessel damage and tissue ischemia where they promote vascular healing and re-perfusion. A growing body of evidence suggests the number and function of EPCs is altered in patients with varying degrees of diabetes duration, metabolic control and in the presence of absence of complications. There is mounting evidence that some EPC sub-types may be involved in the pathogenesis of DR and may also serve as biomarkers for disease progression and stratification. Moreover, some EPC sub-types have considerable potential as therapeutic modalities in the context of cell therapy. This review presents basic clinical concepts of endothelial dysfunction and highlights the potential for EPCs to be used to repair damaged vasculature during diabetes.