Background: Angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphism has been linked to diabetes and the progression of diabetic comorbidities. Objectives: Study the correlation between the ACE I/D gene polymorphism and: a) Risk of development of type 2 diabetes mellitus (T2DM) in Egyptian population. b) Development of diabetic nephropathy. Patients and methods: we studied80 participants: including 20 healthy participants, and 60 patients with diabetes. The following laboratory tests were performed: HA1C, lipid profile, estimated glomerular filteration rate (eGFR), serum creatinine, urine analysis, urine albumin creatinine ratio, DNA Isolation and Determination of ACE Genotype(GT) were performed to all patients and control subjects. Results: In diabetic patients about 81 % had Genotypes II and 18.3% had Genotype ID, while in control group 95 % had genotype II. In diabetics without chronic kidney disease (CKD) 96 % had genotype II and about 3 % had genotype ID. In diabetics with CKD about 66 % had genotypes II while 33 % had genotype ID. There was a significant difference found in the studied groups, p was 0.033. the mean HbA1c, GFR and creatinine in diabetics with chronic kidney disease with genotype II was 7.81,22.57 and 4.08 respectively, while the mean HbA1c, GFR and creatinine in diabetic chronic kidney with genotype ID was 8.92, 13.44 and 5.02 respectively. There was significant difference found in the studied groups according to GFR, p was 0.005. Conclusion The current study demonstrated that; ACE gene I/D polymorphism has potential link to DM and progression to diabetic nephropathy.