Aim To elusidate the effect of tissue-type plasminogen activator(tPA) gene plasmid on prevention of the thrombosis after atherosclerosis.Methods Twenty New Zealand rabbits were divided into two groups(10 for experiment and 10 for control) randomly.All the animals were done with endarterectomy of the iliac arteries and with hypercholesterole feeding after the operation.In experimental group,a 10 cm long gene suture immersed with construced tPA gene plasmid was sutured in the muscle around the injured arteries.All the rabbits were executed 4 weeks after the operation and the local artery pathology including atherosclerosis and thrombosis,the blood D-dimer concentration were observed.Results A model of rabbit iliac artery atherosclerosis was successfully constructed and the transfection of tPA gene plasmid and tPA expression in local muscle tissue arround the injured arteries was obtained effectively.The constructed tPA gene plasmid could inhibit the expressions of PCNA(13.55±8.43 vs 27.78±12.35) and platelet-derived growth factor(PDGF-B) mRNA(3.54±1.78 vs 20.40±11.25) by vascular smooth muscle cell(VSMC) after vascular injury remarkably and could reduce the intimal thickness(32.75±21.50 μm vs 165.70±71.21 μm) and area(0.41±0.47 mm2 vs 2.01±1.15 mm2),and restrict the development of atherosclerosis and lumen thrombosis successfully.Conclusion Constructed tPA gene plasmid could be used for prevention of the thrombosis after rabbit experimental atherosclerosis.