Objective: To investigate the inhibitory effects of the liposome- and adenovirus-mediated early growth response gene-1 DNA enzyme (EDRz) through regional external application on the vascular smooth muscle cells (VSMCs) proliferation and intimal hyperplasia of the autogenous vein graft. Methods: The autogenous vein graft model was established in rats, which were then randomly divided into liposome group, adenovirus group and control group. In vivo transfection was conducted in the two experimental groups by regional application of liposome-EDRz and adenovirus-EDRz on the vein graft, respectively. The vein graft samples were harvested at 1, 2, 6 and 24 hours, and also 3, 7, 14, 28 and 42 days after surgery, respectively. The transfection status of vein graft was detected with fluorescent microscope, Egr-1mRNA and protein expression was measured by in situ hybridization and immunohistochemical staining, respectivcely. Meanwhile, the histomorphology of the vein graft was also observed. Results: At one hour after surgery, EDRz was mainly located in media, adventitia and part of endothelial cells of the vein graft. The fluorescent intensity of liposome group and adenovirus group was 70.3±13.5 and 60.5±11.2, respectively. In 2 to 24 h after surgery, EDRz was located in the media of the vein graft, and it was mainly located in the intima of the vein graft at 7 h after surgery. No EDRz was detected in the vein grafts at the later postoperative period. In the early postoperative period, Egr-1 protein mainly expressed in the medial VSMCs, and in some monocytes and endothelial cells, but it could not be detected in either the media or neointimal VSMCs of the vein graft at the later postoperative period. At 2 h after surgery, the positive expression rate of Egr-1 protein of liposome group and adenovirus group was (15.3±4.2)% and (20.7±2.6)%, respectively. The degree of proliferation of VSMC and intima thickness of liposome group and adenovirus group were obviously decreased compared with control group. Conclusions: EDRz has inhibitory effect on VSMCs proliferation and intimal hyperplasia of the autogenous vein graft through its Egr-1 expression. Liposome transfection is more efficient than adenovirus transfection.