Recent research is now focusing on the role of epigenetic factors, which by themselves and/or in combination with classical genetic factors, may be the major causative factor for progression of diabetic foot ulcer (DFU). The molecular mechanisms that down regulate the NRF2 expression in Type 2 diabetes mellitus (T2DM) and DFU remain unresolved. Aim: to investigate potential association of Nrf2 gene polymorphism with development of DFU. Methods: This case-control study included 81 subjects who were categorized into three groups; group 1 included 27 healthy individuals as a control group, group 2 included 27 type 2 diabetic patients without diabetic foot ulcer and group 3 included 27 type 2 diabetic patients with diabetic foot ulcer. Genotyping of NRF2 (rs35652124) single nucleotide gene polymorphism was done by by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: In the diabetic foot ulcer group, CC genotype was present in 1 (4%) cases, CT and TT genotypes were in 13 (48) and 13 (48%) cases. CT and TT genotypes of NRF2 were significantly higher in diabetic foot ulcer group compared to controls. There was significant difference between diabetic foot ulcer cases and controls regarding to T allele of NRF2 that was higher in diabetic foot ulcer cases than control. There was significant difference regarding C and T allele that was higher in diabetic foot ulcer group than T2DM group. Conclusion: TT genotypes of NRF2 were also higher in case of DFU compared to T2DM. T allele is significantly higher in DFU patient group than only diabetic groups, Nrf2gene has a proper value in prediction of T2DM and development of diabetic foot ulcer in patients with T2DM.