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Background Placement of an extal support has been reported to prevent intimal hyperplasia of vein grafts. However, it is limited by potential complications. In the present study, we investigated the effect of fibrin glue on preventing vein graft failure as perivenous application. Methods Twenty-four rabbits were divided into non-supported group (n=12) and fibrin glue group (n=12). All animals underwent unilateral jugular vein into common carotid artery interposition grafting and then fibrin glue was applied as perivenous support. Samples of tissues were harvested after 4 weeks. Results The vein grafts with fibrin glue demonstrated a statistically significant decrease in proliferating cell nuclear antigen in the medial/intimal region [13.38% (11.26%－15.11%)] compared with non-supported vein grafts [31.22% (27.15%－35.98%)] (P<0.001). Light microscopy showed remarkable attenuation of endothelial cell loss and numerous microvessels in neoadventitia in the fibrin glue group compared with the non-supported group. The smooth muscle cells migrated into adventitia significantly in fibrin glue group, whereas the smooth muscle cells migrated into intima in non-supported group.Conclusion Perivenous support of vein graft with fibrin glue in vivo can attenuate the severe injury encountered in the non-supported vein grafts exposed to artery.