Background Diabetic foot ulcer (DFU) is a common, complex, and costly complication of diabetes that affects the lower extremities. Foot ulceration is the most frequently recognized issues in this disease. The vascular endothelial growth factor (VEGF), encompassing 14 kb, is located on chromosome 6p21.3, and contains 8 exons and 7 introns. There are at least 25 different single nucleotide polymorphisms (SNPs) in the VEGF that are associated with DFU, the current study deals with the most frequent and important one, the rs699947. Objective To investigate the molecular basis of the SNP (rs699947) (-2578C>A) and its correlation with biochemical parameters, such as HbA1c, GSH and MDA, in patients with DFU, in the Kerbala province of Iraq. Materials and methods This study was a cross-sectional study, including 240 subjects of both sexes, which are randomly selected. Subjects were divided into two groups, 120 had DFU and 120 had type 2 diabetes (T2DM), as a control group. The VEGF genotyping was performed by the amplification refractory mutation system- Polymerase Chain Reaction (ARMS-PCR) of DNA, extracted from peripheral blood mononuclear cells of 120 unrelated patients, and 120 unrelated control donors. Results The VEGF polymorphism (rs699947) has a significant association with DFU. The AC genotype significantly raised the risk of DFU (p value ≤ 0.01), but the C allele was more effective in this increase (p value ≤ 0.01). The correlation of AA, AC and CC genotypes of the VEGF polymorphism (rs699947) with biochemical parameters, such as HbA1c, GSH and MDA was significant (p value ≤ 0.01), comparing patients with DFU, and T2DM as a control group. Conclusion A significant association was found between the VEGF polymorphism (rs699947) and DFU, in comparison with the T2DM, as a control group.