Background: Diabetes mellitus (DM) causes elevated blood sugar levels and over time can cause problems of the heart, blood vessels, kidneys, retina, and nervous system. One of the most severe complications of diabetes, diabetic foot ulcers (DFU) are a major factor in the majority of non-traumatic lower-limb amputations. A heterodimer of HIF-1α and HIF-1 β, hypoxia-inducible factor I (HIF-1) is a transcription factor that is stabilized by hypoxia and acts as a fundamental regulator of oxygen homeostasis and adaptive cellular responses to hypoxia. Objective: The current study aimed to evaluate the risk factors of DFU and investigate the serum level of hypoxia inducible factor 1 alpha as biomarker for incidence of DFU. Patients and methods: The study was conducted on 80 patients. Participants were divided into two groups: Group I (diabetic foot) subdivided according to Wagner Meggitt 1987 Classification into grade (0), grade (1), grade (2) and grade (3). Each group included 10 patients. Group II patients (control group) included 40 healthy subjects. Patients were subjected to detailed history and complete examination, and complete laboratory evaluation which included serum Hypoxia- inducible factor I alpha. Results: The associated risk factors of DFU identified in our study were peripheral neuropathy, peripheral vascular disease, diabetic nephropathy, age, duration of DM, lack of education about care of diabetic foot and male gender. There was higher level of serum hypoxia inducible factor 1 alpha in diabetic patients than control subjects with significant increase in DFU patients. Conclusion: HIF-1α may have a role in pathogenesis of DFU.