Background Receptor for advanced glycation end products (RAGE) play an important role in the process of type 2 diabetes and its microvascular complications.RAGE gene Gly82Ser exists polymorphism,but the correlation of gene polymorphism and diabetic retinopathy (DR) needs further research.Objective This study was to investigate the association of Gly82Ser polymorphism of RAGE gene with DR in Han people of Wuxi area with type 2 diabetic mellitus.Methods One hundred and eighty-five patiens with type 2 diabetes were included in Wuxi district from March 2013 to February 2014.The patients were divided into non DR (NDR) group (93 cases) and DR group (92 cases) according to the DR International Clinical Classification Criteria in 2002,and 120 healthy subjects were included at the same time as the control.All of the subjects received eye examinations,body mass index (BMI) and blood pressure measurement as well as laboratory tests,including blood biochemical indexes,blood lipids and fasting blood glucose levels.The peripheral blood of 3 ml was collected from each subject,and the genotype and allelic frequencies were assayed by PCR-direct sequencing.This study protocol was approved by Ethic Committee of Nanjing Medical University.Written informed consent was obtained from each subject prior to any medical examination.Results The course was significantly longer in the DR group than that in the NDR group (t =2.25,P =0.01).There were two alleles of G and A in the RAGE gene Gly82Ser locus in all the subjects and the distribution of single nucleotide polymorphism was in accordance with Hardy-Weinberg equilibrium (DR group:x2 =0.51,P =0.48;NDR group:x2 =1.38,P =0.24;healthy control group:x2 =0.20,P =0.24).The AA genotype frequency of the subjects in DR group,NDR group and healthy control group were respectively 6.5％,3.2％ and 2.5％,and AA genotype frequency in DR group was higher than that of the NDR group and healthy control group,showing significant intergroup differences (x2 =5.146,P =0.023;x2 =5.039,P =0.037).The distribution of A allele frequency in the DR group was significantly higher than that of NDR group and healthy control group (x2=5.494,P=0.019;x2 =5.235,P =0.023),and the frequencies of G allele and GG genotype in the DR group were lower than those of the NDR and the healthy control group (GG:x2 =4.260,P =0.039;x2 =4.794,P =0.027;G:x2 =5.309,P =0.021;x2 =5.476,P=0.032).No significant differences were seen in the frequencies of genotype and allele of subjects between the NDR group and the healthy control group (AA:x2 =5.346,P=0.127;GG:x2 =6.981,P=0.137;A:x2 =5.618,P =0.082;G:x2 =4.860,P =0.088).Conclusions The Gly82Ser polymorphism of RAGE gene is associated with the pathogenesis of DR in Han population with type 2 diabetes and A allele may be a risk factor of DR.