Elevated intermediate-density lipoprotein (IDL), a remnant lipoprotein, is an independent risk factor for atherosclerosis in patients with end-stage renal disease (ESRD). Since the presence of diabetes mellitus further increases the risk of cardiovascular mortality in ESRD, we examined the effect of diabetes on IDL among ESRD patients. The subjects were 330 healthy control subjects and 287 patients with end-stage renal disease including 80 patients with type 2 diabetes. As compared with the healthy subjects, the nondiabetic ESRD patients had increased plasma triglyceride and IDL cholesterol. Diabetic patients with ESRD showed a further increase in plasma triglyceride and IDL cholesterol compared with the nondiabetic group. However, the difference in IDL levels between the ESRD groups was no longer significant when subjects were stratified by plasma triglyceride. Plasma triglyceride was correlated with IDL cholesterol. Increased hemoglobin A(1c) was significantly associated with IDL cholesterol in a multiple regression model including age, gender, and the presence of ESRD. Such an association was no longer significant in another model including plasma triglyceride as an additional covariate. Further analysis indicated the positive effects of diabetes and hyperglycemia on plasma triglyceride. These results indicate that increased IDL in ESRD is further deteriorated in the presence of diabetes, and that the adverse effect is accounted for at least partly by hypertriglyceridemia associated with chronic hyperglycemia.