Twenty to forty percent of type-2 diabetic patients (DM2) present nephropathy. Genetic polymorphism of Apolipoprotein E (Apo E) has been proposed as a risk factor in the development and progression of diabetic nephropathy. The purpose of the study was to evaluate the relationship between Apo E polymorphism and presence of nephropathy in DM2 patients. We studied 85 DM2 patients with a similar nutritional state, environmental and socioeconomic condition and more than 10 years of evolution. They were grouped in DM2 patients with kidney complications (n=56) and without kidney complications (n=29; control group). Apo E genotype was determined by restriction fragment-length polymorphism analysis. A plasmatic biochemical characterization was performed on all the subjects studied. The 85 DM2 patients had arterial hypertension in treatment. The nephropathy diabetic group showed differences (p<0.001) in BMI, systolic blood pressure, glycemia, cholesterol (total, HDL and LDL), HbA1c and creatinine. The e4 allelic frequency was 8% in the nephropathy group versus 25.9% in the control group. Apo e3 allele and E3/3 genotype frequency were higher and E3/4 genotype was lower in the nephropathy group than in controls. These groups also showed differences in total, HDL and LDL cholesterol. DM2 patients without nephropathy presented a higher frequency of e4 allele. These results could suggest a protective role of e4 allele in the development and progression of diabetic nephropathy.