Diabetic microangiopathy is a slowly progressive condition that usually manifests itself years after the onset of the carbohydrate-metabolism disturbance. It is a far more striking problem in some diabetics than in others. Differences in the pattern of its effect in several body systems suggest that the local vascular disturbance is a mixture of a general microcirculatory change in diabetes and a specific vascular alteration in each tissue. Its manifestations in the individual diabetic appear to be influenced by both elements. Evidence is presented that plasma protein changes in diabetes and their effects on blood flow play a role in acclerating the rate of progression of diabetic microangiopathy by raising plasma viscosity and by increasing the affinity of erythrocytes for each other. The plasma protein change is dominated by a possibly hormonally mediated pattern of alpha-globulin elevation seen in many chronic disorders. This elevation of acute-phase proteins is not likely by itself to produce diabetic microangiopathy, but it may cause an additional stress on the metabolically disturbed diabetic microcirculation. The basic change is a disturbance in the average molecular shape of the plasma proteins that both directly increases plasma viscosity and enhances the aggregation of erythrocytes. Studies are now in progress to determine which of these two mechanisms is more likely to be important in accelerating the development of diabetic microangiopathy.