The high plasma glucose concentrations in patients with diabetes are associated with an increased risk of vascular disease. In patients with non-insulin-dependent diabetes mellitus, vascular changes often predate clinical diagnosis of hyperglycaemia. Impaired glucose tolerance precedes diabetes and may therefore be an important phase in the development of vascular changes. There is evidence to suggest that hyperglycaemia interferes with the activity and function of endothelial cells. In vitro data show that high glucose concentrations can activate protein kinase C (PKC) in endothelial cells, specifically PKC β£. This activation appears to stimulate expression of adhesion molecules on endothelial cells, facilitating the adhesion and uptake of leukocytes into the endothelium. In addition, high glucose concentrations affect the permeability of tight junctions between endothelial cells, which also seems to be mediated by PKC. Thus, PKC activation may be central to the effects of glucose-stimulated vascular changes. Evidence for direct stimulation of endothelial cells by glucose may support the hypothesis that postprandial glucose spikes are important in the early development of micro-and macrovascular disease.