Vein graft remains the most broadly applied vascular material in coronary artery bypass surgery. However, the restenosis rate of the vein bridge following angioplasty is high. The present study investigated the effect of medical adhesive on vascular intimal hyperplasia, in addition to the signal transduction mechanism. A total of 36 New Zealand white rabbits were divided into three groups at random, including the normal group, the surgery group and the medical adhesive spray group. Following surgery for transplantation of the left external jugular vein to the ipsilateral common carotid artery for 4 weeks, the thickness and area of the intima and media of the vessel were measured on formalin-fixed, paraffin wax-embedded pathological sections using hematoxylin-eosin staining, and alterations in the expression of proliferating cell nuclear antigen (PCNA), platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion protein 1 (VCAM-1), extracellular signal-regulated kinase (ERK)1/2, and endothelial nitric oxide synthase (eNOS) were detected by immunohistochemical staining, reverse transcription-quantitative polymerase chain reaction analysis and western blotting. The levels of intimal hyperplasia in the medical adhesive spray group were markedly decreased compared with the surgery group. Consistently, PCNA, PECAM-1 and VCAM-1 were underexpressed in the medical adhesive spray group compared with the surgery group. ERK1/2 and eNOS were underexpressed in the medical adhesive spray group compared with the surgery group. Therefore, the application of medical adhesive may inhibit intimal hyperplasia, which may be associated with the restriction of the over-distension of the vein graft by downregulating the ERK1/2 and eNOS levels, reducing injury to the vascular intima and inhibiting the signaling pathway involved in intimal hyperplasia.