Background: The molecular mechanisms that downregulate the nuclear factor erythroid related factor 2 (NRF2) expression in addition to gene polymorphism among type 2 diabetes mellitus (T2DM) patients. Objective: To investigating possible association between NRF2 gene polymorphism with T2DM development. Patients and Methods: This case-control study included 81 persons who were categorized into three groups; The first group, made up of 27 healthy people, served as a control, group 2 consisted of twenty-seven type 2 diabetics without foot ulcers, and group 3 consisted of twenty-seven patients with diabetic foot ulcer who had type 2 diabetes. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to do genotyping of NRF2 (rs35652124) single nucleotide gene polymorphism. Results: Concerning NRF2 genotyping in the investigated groups, 18 (67%) of controls possessed the CC genotype, while 7 (26%) possessed the CT genotype, and 2 (7%) possessed the TT genotype. Eight (30%) of cases in the cases group had the CC genotype, while 13% had CT genotype and 48% had TT genotype. Cases had a far higher frequency of the CT and TT genotypes than controls did. In terms of NRF2 allele distribution, we found that although 43 (80%) of controls and 11 (20%) of controls carried the C allele, 29 (54%) of patients carried the C allele and 25 (46%) of cases carried the T allele. T2DM patients had a significantly greater frequency of T alleles than control subjects. Conclusion: Regarding NRF2 genotyping, our study revealed that TT genotypes and T alleles were statistically significantly higher among patients' group (diabetic with and without diabetic foot) compared to controls. NRF2 gene has a proper value in prediction of T2DM.