To assess the relationship between IGF-I gene polymorphism and incident diabetic retinopathy, fundus color transparencies were taken at baseline (1990 - 1993) and at follow-up (1997 – 1999) in 775 subjects with impaired glucose tolerance (IGT), 394 subjects with type 2 diabetes and 4336 control subjects, with 72.2% of participants carrying the wild-type genotype and 27.3% being variant carriers. Compared with wild-type genotype subjects, retinal arteriolar and venular diameters at baseline tended to be larger in variant carriers, especially in subjects who developed retinopathy at follow-up. Further, in variant carriers with IGT/diabetes, there was a significant [OR = 1.8, CI (1.0 – 3.2), P = 0.04] increase in the risk of retinopathy compared with wild-type genotype subjects.