We investigated the relationship between apolipoprotein E (apoE) gene common polymorphism (E2, E3, and E4) and diabetic vascular complications in 166 Japanese patients with Type 2 diabetes mellitus (T2DM) (79 men and 87 women, age 61.6+/-0.7 yr, duration 14.9+/-0.5 yr, mean+/-SE). Allele frequencies of E2, E3 or E4 were 4.2%, 86.5 % or 9.3 %, respectively, and not significantly different from those of 94 non-diabetic controls (E2:5.8 %, E3:86.7%, E3:86.7%, E4:7.5 %). We divided T2DM patients into three groups according to apoE genotype; E2 group (E2/E2 and E2/E3), E3 group (E3/E3), and E4 group (E3/E4 and E4/E4), Among these three groups, there were no significant differences in age, sex, duration of T2DM, body mass index, HbA(1c) and plasma lipid levels (total cholesterol, HDL cholesterol, and triglyceride), In the frequencies of hypertension, hyperlipidemia, ischemic heart disease, and nephropathy, no significant differences were observed among the three groups. In contrast to them, the frequency of preproliferative/proliferative retinopathy in the E4 group was significantly higher than that in the others. Our results suggest that apoE gene E4 allele is a risk factor of diabetic retinopathy in Japanese T2DM patients.