In this study, we prepared a composite vascular graft with two layers. The inner layer, which was comprised of degradable Poly(lactic-co-glycolic acid) (PLGA)/Collagen (PC) nanofibers modified by mesoporous silica nanoparticles (MSN), was grafted with polyethylene glycol (PEG) and heparin to promote cell proliferation and to improve blood compatibility. The outer layer was comprised of polyurethane (PU) nanofibers in order to provide mechanical support. The growth and proliferation of human umbilical vein endothelial cells (HUVECs) in the inner layer was significant, and blood compatibility testing showed that the inner layer had good blood compatibility. The MSN-PEG-Heparin on the fiber surface was observed in vitro during the degradation of the inner layer. After 60 days, the weight of fiber membrane decreased by 92.4%. The inner layer did not cause an inflammatory reaction during the degradation process in vivo and there was uniform cellular growth on the PC/MSN-PEG-Heparin fiber membrane. Composite grafts implanted into the rabbit carotid artery were evaluated for 8 weeks by H&E and immunohistochemical staining, demonstrating that a monolayer of endothelium (CD31-labeled) and smooth muscle (αSMA-labeled) regenerated on the composite graft. Our results demonstrate that the composite graft, with a functional inner layer, has potential to be used for small-caliber blood vessels with long-term patency.