The results indicated that VEGF expression is regulated by HIF1α under hypoxia conditions, and the expression of either ERβ or SOD2, or ERβ agonist DPN treatment, diminishes hyperglycemia-induced persistent ROS generation, activates HIF1α transcriptional activity, and subsequently upregulates VEGF expression, favoring wound healing. This evidence concerns the gene HIF1A and Hyperglycemia.