Vascular grafts are significantly needed in peripheral vascular surgery; however, small diameter grafts are not always available, and synthetic grafts perform poorly because of acute thrombosis and neointimal proliferation after implantation. This study used electrospun poly-epsilon-caprolactone (PCL) as the matrix material to build a small-diameter vascular graft. Organoselenium modified polyethyleneimine (SePEI), which can catalyze the production of nitric oxide from S-nitrosothiols, and heparin (Hep) were introduce through layer-by-layer (LbL) assembly in order to prepare a new vascular graft with improved histocompatibility and biological function. Static water contact angle measurement showed that SePEI and Hep had improved the hydrophilicity of the material, which is desirable for an active vascular graft. The results showed that the mechanical property and histocompatibility of the SePEI/Hep loaded material could meet the demands of vascular grafts. The results of cellular experiments showed that the SePEI/Hep loaded material could promote the proliferation and adhesion of endothelial cells, which is beneficial to the rapid endothelialization of vascular grafts. And this material could inhibit the adhesion and spreading of smooth muscle cells, which can prevent the post-implantation restenosis. The SePEI/ Hep loaded material could inhibit the activation of macrophages, which is very important in reducing inflammation following graft implantation.