The vascular adventitia is layered with loose connective tissue, which includes external elastic lamina, vasa vasorum, and nerve ending. Fibroblasts are the main cellular components of the adventitia. In the previous studies, the vascular adventitia is considered to only play roles in nourishing blood vessels and maintaining the tension and structure of blood vessels. Recent studies have found that vascular adventitia secretes a variety of bioactive polypeptides as an autocrine/paracrine manner. These bioactive polypeptides play a vital role in the maintenance of vascular homeostasis and vascular injury diseases such as atherosclerosis, abdominal aortic aneurysm, hypertension, pulmonary arterial hypertension, vascular calcification and restenosis after angioplasty. Paying attention to and strengthening the research on the biological effects of paracrine/autocrine bioactive polypeptides from vascular adventitia and their roles in the maintenance of vascular homeostasis and injury diseases has important significance for the maintenance of vascular homeostasis and the understanding of the pathogenesis of vascular injury diseases.