Background: Genetic factors play important role in the development of type 2 diabetes and diabetic nephropathy. Endothelial nitric oxide synthase (eNOS) gene is responsible for the bioavailability of nitric oxide and endothelial function. Aim: To assess the association of the endothelial nitric oxide synthase (eNOS) (T786C and G894T) single nucleotide polymorphisms with Egyptian type 2 diabetes mellitus and diabetic nephropathy. Patients and methods: A total of 200 type 2 diabetic patients and 100 apparently healthy volunteers as controls were included in the study. They were subjected to clinical examination and laboratory tests: fasting blood glucose, HBA1C, lipid profile, serum creatinine, blood urea and albumin creatinine ratio (ACR). Assessment of the T786C and G894T polymorphisms in the eNOS gene was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: There was no significant difference in distribution of eNOS T-786C polymorphism between patients and controls; TT genotype of eNOS G894T was more frequent in diabetic patients with and without albuminuria compared to controls. Patients were divided into 3 groups according to ACR. Normoalbuminuria: 37 patients with ACR ≤ 30 mg/g, microalbuminuria: 96 patients with ACR > 30 mg/g and ≤ 300 mg/g, and macroalbuminuria: 67 patients with ACR > 300 mg/g. There was no significant difference in genotype distribution of eNOS T-786C between the 3 groups of diabetic patients. The prevalence of TT genotype of eNOS G894T was higher in microalbuminuria patients compared to other groups. Conclusion: eNOS G894T variant may increase risk of type 2 diabetes with lack of association between eNOS T786C, eNOS G894T and DN in Egyptians.