A 66-yr-old man with non-insulin-dependent diabetes mellitus complicated by retinopathy and nephropathy presented with shortened red cell survival associated with prominent fragmentation of erythrocytes and leading to severe hemolytic anemia. Neither abnormal carbohydrate tolerance per se nor renal failure was related to the red cell fragmentation syndrome. Also, a marked platelet hyperaggregability, which disappeared under treatment with ticlopidine, was demonstrated. Furthermore, during treatment with this potent platelet inhibitor, red cell survival normalized and all signs of hemolysis, as well as the schistocytes present in the peripheral blood smears, disappeared. Two weeks after stopping ticlopidine administration, microangiopathic hemolytic anemia relapsed. We suggest that the fragmentation hemolysis in this patient was related to diabetic microangiopathy, and that the beneficial effects of ticlopidine are related to its platelet-inhibiting activities. This case further reaffirms that antiplatelet agents may have a beneficial effect on the vascular disease of diabetes mellitus.