The aim of this study was to look for a relationship between the - 429 T/C and the - 374 T/A gene polymorphisms of the receptor of advanced glycation end products (RAGE) gene and the development of diabetic retinopathy in Caucasians with type 2 diabetes.One hundred and sixteen subjects with type 2 diabetes and diabetic retinopathy were compared to 70 diabetic subjects without diabetic retinopathy. Additionally, 76 subjects with proliferative diabetic retinopathy (a subgroup of diabetic retinopathy) were compared to 70 diabetic subjects without diabetic retinopathy.The - 429 T/C and the - 374 T/A RAGE gene distributions in patients with diabetic retinopathy (- 429 T/C: CC 0.9%, TC 25.9%, TT 73.2%; - 374 T/A: AA 9.5%, TA 47.4%, TT 43.1%) were not significantly different from those of diabetic subjects without retinopathy (- 429 T/C: CC 0%, TC 25.7%, TT 74.3%; - 374 T/A: AA 15.7%, TA 42.9%, TT 41.4%). Moreover, the - 429 T/C and the - 374 T/A RAGE gene distributions in patients with proliferative diabetic retinopathy were not statistically significantly different from those in diabetic subjects without retinopathy.Our study failed to demonstrate an association between either - 429 T/C or - 374 T/A gene polymorphism of the RAGE gene and diabetic retinopathy in Caucasians with type 2 diabetes. Additionally, we failed to demonstrate an association between either - 429 T/C or - 374 T/A gene polymorphism of the RAGE gene and proliferative diabetic retinopathy in Caucasians with type 2 diabetes.