Diabetic nephropathy is a polygenic and multifactorial disease. Studies of familial clustering and genetic predisposition suggest that genetic factors are involved. Among candidate genes, the coding for angiotensin-converting enzyme (ACE) polymorphism has been described. Our objective was to investigate the association ACE gene insertion/deletion (I/D) polymorphism with the development of diabetic nephropathy in a Mexican population. In a cross-sectional study, we evaluated 204 patients with type 2 diabetes: 43 with incipient diabetic nephropathy, 45 with established diabetic nephropathy and 116 without diabetic nephropathy. Diabetic nephropathy was defined according the American Diabetes Association criteria. The ACE I/D gene polymorphism was detected by polymerase chain reaction. Patients with type 2 diabetes with both incipient diabetic nephropathy and established diabetic nephropathy significantly differed from controls with respect to variables that determined kidney damage (P