We investigated the relationship between the -460T/C and -1154G/A polymorphisms in the promoter region of the vascular endothelial growth factor (VEGF) gene and diabetic foot ulcer (DFU) in a northern Han Chinese population. A total of 209 type 2 diabetes mellitus (T2DM) patients were examined in this hospital-based case-control study. Polymerase chain reaction-restriction fragment length polymorphism was used to detect polymorphisms at the -460T/C and -1154G/A loci of the VEGF gene promoter in 94 healthy controls and 209 T2DM patients, including 112 cases of T2DM alone and 97 cases of T2DM with DFU. Genotype and allele frequencies in each group were compared. Patients and controls exhibited no significant differences in polymorphisms at the -1154G/A locus of the VEGF gene promoter. However, at the -460T/C locus, the C allele was observed with significantly lower frequency in DFU patients than in patients with T2DM alone (T/C + C/C vs T/T, P=0.0109, OR=0.4708, CI: 0.2625-0.8444). The C allele was also observed significantly less frequently in DFU patients than in control group patients (P=0.0037, OR=0.4784, CI: 0.2891-0.7916). This study demonstrated that the C allele of the -460T/C polymorphic locus is present at a lower frequency in DFU patients than in other individuals. This may reflect the protective role of this allele in increasing angiogenesis in patients.