Background: Diabetic foot ulcer (DFU) is one of the most distressing complications in patients with type 2 diabetes mellitus (T2DM). Vascular endothelial growth factor (VEGF) is a strong angiogenic factor associated with wound healing and development. Aim: This study aimed to investigate the miR-200b and VEGF mRNA levels in patients with T2DM and to discover their relations with the clinicopathological and anatomical distribution of DFU. Methods: This case-control study enrolled 70 patients with T2DM and 70 healthy subjects as controls. Physical and neurological examination to assess the Wagner classification. RT-PCR was done to assess miR-200b and VEGF mRNA expression levels. Results: there were significantly higher values of VEGF mRNA levels in patients with DFU (3.13±1.87) compared to patients without DFU (2.41±0.197) and controls (1.07±0.363), with P value ˂0.001* Additionally, miR-200b levels were significantly higher in patients with DFU (3.48±1.47) compared to patients without DFU (2.94±0.187) and controls (1.13±0.37), with P value ˂0.001*. The power of VEGF mRNA and miR-200b levels as a diagnostic marker for DFU were projected (2.5 and 3.1, respectively), which yielded a sensitivity of (77.1% and 74.3, respectively) and a specificity of (77.3% and 75.2%), with the AUC at (0.886 and 0.845, respectively) . The size of DFU in cm was 3.5±0.421 and the number of ulcers was 2.45±0.433. Conclusion: the VEGF mRNA and miR-200b levels were significantly higher in patients with T2DM, particularly those with DFU. Consequently, we believed that VEGF mRNA and miR-200b may serve as promising predictive biomarkers for diabetes and DFU.