In this study we tested the hypothesis that the Leu7Pro7 polymorphism in prepro neuropeptide Y (NPY) gene could be a risk marker for the development of diabetic retinopathy and analyzed a well characterized cohort of patients with Type 2 diabetes followed-up for 10 years from the time of diagnosis. The frequency of Leu7/Pro7-polymorphism was 9.3% (8 out of 86). At baseline, the frequency of retinopathy in patients with the Leu7/Pro7-polymorphism was 25% (2 out of 8) and in those without it 6.4% (5 out of 78) (p=0.126). At 10-year the respective figures were 88% and 50% (p=-0.040). The odds ratio for Leu7/Pro7-polymorphism in logistic regression analysis adjusted for age, gender and HbA1c was 8.97 (95% confidence intervals 1.09-98.0; p=0.049). Our finding based on elderly Finnish Type 2 diabetic subjects suggests that the Leu7Pro7-genotype in preproNPY gene is associated with the development of diabetic retinopathy.