In present study, we found that db/db mice presented higher UACR, more significant renal histological damage, and more significant podocyte injury than db/m mice, renal fibrosis and apoptosis were elevated in db/db mice compared with db/m mice, and the more significant endothelial dysfunction and the increased levels of HIF-1α and Notch1 in db/db mouse kidneys compared with db/m mouse kidneys. The gene discussed is HIF1A; the disease is endothelial dysfunction.