Both the disruption of endothelial homeostasis and tissue fibrosis are characteristics of diabetic complications. Accumulating evidence has revealed the significant role of vascular endothelial cells in tissue fibrogenesis via endothelial-mesenchymal transition （EndMT）.
We have recently focused on the overexpression of endothelial dipeptidyl peptidase （DPP）-4, a critical pathological feature of the molecular mechanisms of EndMT, and suggest that DPP-4 inhibitors have great therapeutic potential via their antifibrotic effects. However, the diverse pleiotropic effects of DPP-4, both its enzyme-dependent and enzyme-independent effects, can be detrimental in some cases. This review provides an update on the biology of DPP-4, a profibrotic molecule, in addition to a discussion of cancer biology.