The Notch signaling pathway is involved in multiple mechanisms in DKD, including glomerular endothelial dysfunction, filtration barrier damage, podocyte EMT and dedifferentiation, tubulointerstitial fibrosis, proximal tubule cell dedifferentiation, macrophage polarization, etc. In addition, Notch signaling interacts with other pathways involved in DKD progression, such as TGF-β, Wnt/β-catenin, mTOR, AMPK, autophagy, etc. Therefore, new ideas for the future treatment of DKD may be provided through clarification of the role of the Notch signaling pathway and development of novel drugs. This evidence concerns the gene TGFB1 and endothelial dysfunction.