Major susceptibility factors for diabetic microangiopathy include duration of disease and probably quality of metabolic control. The mechanism of development of microangiopathy is incompletely understood but appears to involve functional abnormalities within the microcirculation, enhanced glucose metabolism, hemostatic abnormality, and genetic susceptibility. This article reviews the factors believed to be involved in pathogenesis and attempts to draw these together by suggesting a sequence of pathogenic interactions that could result in the microvascular changes seen in susceptible target organs. Possibilities for therapeutic intervention based on these pathogenic mechanisms are discussed. A small pilot trial of an oral hypoglycemic agent, gliclazide, is reported, providing evidence for a specific action of this drug on thromboxane synthesis and platelet aggregation. This is independent of glycemic control and may in part be mediated by a fall in lipid peroxides.