Aim To investigate the effects of in vivo local transfection of zinc finger protein A20 gene on restenosis of balloon injured rat carotid artery and its possible mechanism. Methods Balloon catheter denudation of the endothelium of rat common carotid artery was routinely used as a model of restenosis.104 male Sprague-Dawley rats were randomly divided into 4 groups: the sham group(no injury),the model group(the simple injury),the control group(vacant transfection regent group) and the therapeutic group(A20 gene and transfection regent group).pCAGGS-GFP/A20(20 μg) with 40 μL Lipofectamine 2000 or TE buffered solution(20 μL) with 40 μL Lipofectamine 2000 was instilled into the lumen of the injured segment for 30 min after injury.The transfection efficiency of plasmid in injured vascular wall was evaluated 24 hours after transfection by using fluorescence microscope.Quantification of intimal hyperplasia was determined by pathologic examination.Proliferation index of VSMC in vivo was assessed by thymidine analogue bromodeoxyuridine(BrdU) labeling technique.The expression of nuclear factor-kappaB p65(NF-κBp65) of rat carotid arteries in different groups were confirmed by immunohistochemical staining and Western blot analysis. Results At day 14 significant intimal hyperplasia was detected after arterial injury in the model and control group.A20 gene transfection markedly reduced the neointimal area(47.8% reduction;P<0.05) and intimal to media area ratio(42.9% reduction;P<0.05) in the therapeutic group.Proliferation index of VSMC(BrdU index) at day 10 after operation was decreased significantly in the therapeutic group(9.6%±2.3%) than in the control group(26.7%±5.1%,P<0.05).A significantly lower level of NF-κBp65 positive cells ratio was observed in the therapeutic group than in the control group at 10d after operation(P<0.05).A significantly lower level of NF-κBp65 protein expression was observed in the therapeutic group than in the control group at day 7 d,14 d,28 d after operation(P<0.05).Conclusion Local transfection of A20 gene inhibits intimal hyperplasiaand VSMC proliferation after arterial injury.Its possible molecular mechanism is that A20 negative feedback inhibits NFκ-B sig-naling pathway.This study provides evidence for the inflammatory mechanism of restenosis and suggests that A20 gene therapymay serve as a novel gene therapeutic approach to inhibit restenosis.