Objectives: The extracellular matrix (ECM) has been widely used in regenerative medicine, obtaining excellent outcomes. However, as a perivenous support material, it has not been studied yet. The current study aimed to test the effects of ECM external stents (ES) in intimal hyperplasia of vein grafts, exploring its underlying mechanisms. Methods: Thirty-six New Zealand white rabbits were randomized into three groups: no-graft group, graft group, and ES group (n = 12 in each group). Four weeks after the operation, histological characteristics of vein grafts were evaluated. Additionally, mRNA and protein levels of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-2 (TIMP-2) were measured by quantitative real-time polymerase chain reaction and Western blotting. Results: Compared with the graft group, the ES significantly mitigated intimal hyperplasia (P < 0.05) and inhibited dilatation (P < 0.05) of vein grafts. Similarly, the ES also markedly inhibited the degradation and remodeling of collagen in the intima and media of vein grafts. In the ES group, it was found that up-expression of PCNA in the intima and media of vein grafts was inhibited (P < 0.05). Quantitative mRNA and protein evaluations revealed a lower expression of MMP-2 (P < 0.05) and a higher expression of TIMP-2 (P < 0.05) in the ES group, compared to the graft group. Conclusion: ECM ES exerts beneficial effects in the intimal hyperplasia of vein grafts. These beneficial effects may be associated with reducing the proliferation of vascular smooth muscle cells and maintaining the balance of MMP-2/TIMP-2.