Effective therapies to prevent vein graft failure after coronary artery bypass grafting (CABG) are still lacking. alpha-Cyanoacrylate (alpha-CA, 99% n-octyl-alpha-cyanoacrylate + n-butyl-alpha-cyanoacrylate) has been increasingly used as a tissue sealant for wound closure because of its bacteriostatic, biodegradable and haemostatic properties. As a strong tissue adhesive, alpha-CA might prevent an arterial circulation-induced mechanical stretch on vein graft to attenuate intimal hyperplasia. Here, we investigated the effects of perivenous application of alpha-CA on the vein graft in a rabbit model of carotid artery bypass grafting. Healthy New Zealand white rabbits were randomized into no graft, graft or graft + alpha-CA group (n = 10 per group). Rabbit carotid artery was bypassed with the jugular vein. alpha-CA sealants were sprayed on the entire jugular graft including both anastomotic sites after completion of anastomoses. Blood flow parameters and histological characteristics of the vein grafts including vessel wall thickness, number of medial elastic lamina and proliferation index were evaluated 4 weeks after the surgery. The mRNA or protein levels of proinflammatory factors, chemokine (C-C motif) ligand-2 (CCL-2) and tumour necrosis factor-alpha (TNF-alpha) were measured 4 weeks after the operation by quantitative reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay. Compared with the untreated vein grafts at Week 4 after the operation, the alpha-CA spray significantly improved graft flow (39.4 +/- 1.5 vs 27.8 +/- 2.9 ml/min, P < 0.01), attenuated intimal and medial thickening (116.3 +/- 1.0 vs 159.7 +/- 0.9 mu m, P < 0.01), reduced anti-proliferating cell nuclear antigen proliferation index of the vein grafts (15.0 +/- 0.4 vs 23.6 +/- 0.4%, P < 0.01), decreased the mRNA levels of plasminogen activator inhibitor-1 and CCL-2, and reduced the serum levels of TNF-alpha (92.9 +/- 1.7 vs 102.7 +/- 1.8 pg/ml, P < 0.01). Perivenous application of alpha-CA sealants exerts short-term beneficial effects on the vein graft and reduces inflammatory responses in a rabbit model of carotid artery bypass grafting. Long-term effects of alpha-CA on vein graft remodelling and the clinical significance of alpha-CA in CABG remain to be determined in future studies.