In conclusion, results of present investigations showed that hesperidin treatment inhibited diabetes-induced increased blood glucose level and down-regulated VEGF-c, Ang-1/Tie-2, TGF-β and Smad-2/3 mRNA expression to accelerate angiogenesis and vasculogenesis resulted in enhances wound healing in chronic diabetic foot ulcers. This evidence concerns the gene VEGFC and diabetes mellitus.