The alterations in the metabolism of arachidonic acid to prostaglandin I2 (prostacyclin), a vasodilator antiaggregatory substance, and thromboxane A2, a vasoconstrictor proaggregatory substance, in diabetes mellitus are reviewed in this article. When tested in vitro, platelet aggregation is enhanced in some patients with diabetes mellitus. The synthesis of thromboxane B2, the stable metabolite of thromboxane A2, by platelets is increased in patients with diabetes mellitus compared with control subjects. This increased synthesis appears to play a role in the enhanced platelet aggregation since the latter can be reversed by aspirin treatment and in vitro by the thromboxane receptor-antagonist 13-azaprostanoic acid. Vascular prostacyclin synthesis is decreased in both patients and experimental animals with diabetes mellitus. Treatment of experimental animals with insulin reverses the decreased synthesis of prostacyclin. The etiology of the altered arachidonic acid metabolism remains uncertain but appears to be multifactorial and includes alterations in metabolic control and circulating immune complexes. The increased ratio of thromboxane A2 to prostacyclin, which favors an enhanced thrombotic state, may play a role in the accelerated vascular disease of diabetes mellitus.