Patients with diabetes mellitus (DM) have increased mortality and morbidity of cardiovascular diseases compared with non-diabetic patients. The role of apolipoprotain E in lipid metabolism and cholesterol transport is well established. Apolipoprotein E gene (APO E) polymprphism that confers susceptibility to or protection from CAD in patients with type 2 DM may be quite different in different ethnic populations. We aimed to determine the frequencies of allelic variants of APO E in Egyptian population and to examine the relationship between APO E polymorphism and risk of coronary artery disease (CAD) in Egyptian type 2 diabetic patients. The study included 35 diabetic patients with CAD (group 1), 35 diabetic patients without CAD (group II) and 30 control subjects. All were subjected to history taking, clinical examination, and laboratory investigations for lipid profile and APO E genotyping by PCR-RFLP. Results revealed that epsilon3 allele was the commonest among the studied subjects (84%). The frequencies of epsilon2 and epsilon4 alleles were higher in group I (24.3% and 8.6% respectively) than group II and controls. The frequency of E2/E2, E2/E3, and E4/E3 genotypes was significantly higher in group I than group II and controls. Comparing group I vs. controls and group I vs. group II, multivariate analysis demonstrated significantly increased risk for CAD with epsilon4 and epsilon2 alleles vs. E3 (OR=7.02 and 4.97 respectively). In Conclusion, epsilon4 and E2 alleles are associated with higher risk of CAD in type2 DM than epsilon3 allele. Larger scale studies are still needed to either confirm or modify these results.