Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene are associated with diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). Methods: A total of 268 patients with T2DM (129 with DR and 139 without DR) were recruited and enrolled in the study. Patients with T2DM were assigned to a DR group or a diabetic-without-retinopathy group, based on the duration of diabetes and grading of fundus images. Genotypes of eight SNPs in the VEGF gene (rs699947, rs833061, rs13207351, rs2010963, rs833069, rs2146323, rs3025021, and rs3025039) were analyzed using a mass-array genotyping system, and an association study was performed. Results: After adjusting for covariates, a significant association of DR was observed with the homozygous genotype of the minor allele for promoter SNPs rs699947 (odds ratio (OR)=3.54, 95% confidence interval (CI): 1.12-11.19), rs833061 (OR=3.72, 95% CI: 1.17-11.85) and rs13207351 (OR=3.76, 95% CI: 1.21-11.71). A significant association of DR was also observed with haplotype ACA, as defined by minor alleles of promoter SNPs rs699947, rs833061, and rs13207351 (OR=1.52, 95% CI: 1.03-2.24), and haplotype GAA, as defined by SNPs rs2010963, rs833069, and rs2146323 (OR=1.62, 95% CI: 1.08-2.41). Conclusions: Our data suggest that polymorphisms in the promoter region of the VEGF gene increase the risk of DR in Chinese patients with T2DM.