Genetic factors are implicated in the development of diabetic retinopathy, and the aldose reductase (AC)n gene is a candidate gene for the development of diabetic retinopathy in patients with Type 2 diabetes. In the association study, a relationship between the aldose reductase (AC)n gene polymorphism and the development of diabetic retinopathy in patients with Type 2 diabetes were studied. We tested the hypothesis whether the Z-2 allele of the aldose reductase gene is a risk factor for the development of diabetic retinopathy in a group of Caucasian participants with Type 2 diabetes. Two hundred and five participants with Type 2 diabetes were enrolled in the study: 124 participants with Type 2 diabetes with diabetic retinopathy were compared with 81 diabetic participants without retinopathy with diabetes duration of more than 10 years. Eight alleles of the aldose reductase (AC)n gene polymorphism were detected: Z+6, Z+4, Z+2, Z, Z-2, Z-4, Z-6, and Z-8. An increased frequency of the Z-2 allele was found in the patients with diabetic retinopathy compared with the patients without diabetic retinopathy (39.1% vs. 26.5%; P value=.009, chi2=6.9). Our results suggest that the Z-2 allele of the aldose reductase gene is a risk factor for the development of diabetic retinopathy in a group of Caucasian participants with Type 2 diabetes.