Hesperidin ameliorated the increased levels of blood glucose, serum insulin, food intake, and water intake in STZ- induced diabetes. It also had a protective effect on the wound architecture by accelerating angiogenesis and vasculogenesis via the up-regulation of vascular endothelial growth factor c (VEGF-c), Angiopoietin (Ang)-1/Tie-2, transforming growth factor (TGF-β), and small mothers against decapentaplegic (Smad)-2/3 mRNA expression to enhance wound healing in the chronic diabetic foot ulcer condition in the diabetic rats. This evidence concerns the gene INS and diabetic foot.