Several evidences suggest the existence of a genetic background in the occurrence of diabetic nephropathy. To evaluate the possible impact of apolipoprotein E (apoE) polymorphism on the presence of microalbuminuria we investigated the apoE allele distribution and lipid levels in 136 NIDDM patients divided in three groups: 34 Normotensive Normoalbuminuric (NND), 50 Hypertensive Normoalbuminuric Diabetic patients (HND) and 52 Microalbuminuric Diabetic Patients (MD). Age, gender, metabolic control and diabetes duration were similar in the three groups. Compared to a free living population sample, from the same geographic area (493 subjects), apoE4 allele was more frequent in microalbuminuric patients (0.109 vs 0.173, p<0.05), with an increasing frequency going from the NND to the MD group. This observation suggests that apoE gene polymorphism may influence not only atherosclerosis, but also the development of microalbuminuria and diabetic kidney disease. The possible role of apoE polymorphism in macrophages is discussed.