Intercellular adhesion molecule-1 (ICAM-1) is an inflammation cytokine. Previous studies have demonstrated that genetic polymorphisms in the ICAM-1 gene are associated with chronic inflammation and diabetic nephropathy. The present study aimed to investigate the association of ICAM-1 gene polymorphisms with type 2 diabetes (T2D) and diabetic peripheral neuropathy (DPN) in a Chinese Han population. Four valid single nucleotide polymorphisms (SNPs) in the ICAM-1 gene were geno-typed in 672 control subjects, 787 T2D patients with and without DPN with TaqMan allelic discrimination. Single marker association analyses indicated that A allele of SNP rs5498 was associated with DPN (P = 0.037, OR 1.715, 95 % CI 1.027-2.865). Further analyses of clinical parameters according to the genotypes of this polymorphism demonstrated that T2D patients with DPN carrying AA and AG genotypes had higher risk of coronary heart disease compared with those carrying GG genotype (30.6 % vs. 11.5 %, P = 0.040). In SNP rs1799969, the difference of minor allele frequencies between the patients without and with DPN was found (0.02 vs 0.01, P = 0.014, OR 3.695, 95 % CI 1.211-11.277). SNP rs281432 had higher frequency of G allele in all T2D patients compared with control subjects (0.35 vs. 0.31, P = 0.041, OR 1.200, 95 % CI 1.008-1.428). The present study provides evidence that rs5498 (A/G E469K) polymorphism is associated with DPN in T2D, and also implicates that the association of ICAM-1 with DPN may be related to other vascular complications.