Objective To explore phenotypic modulation of vascular smooth muscle cells(VSMC) and change of p38 mitogen-activated protein kinase(MAPK) expression after intimal injury of rabbit carotid arteries. Methods The model of vascular restenosis established by balloon injury of rabbit carotid common arteries was used.HE staining,immunohistochemistry staining and Western blot were used to detect the change of proliferation cell nuclear antigen(PCNA),smooth muscle ?-actin(SM?-actin),p38 expression and morphology of sham-injured arteries and injured arteries at different time points.Results ⑴The proliferating VSMC was observed on the side of the medium lumen at 1 day and on the surface of vascular lumen at 3 days after injury.The neointima was formed and gradually being thicken at 5～7 days,and the thickening was accelerated at 14～35 days after injury.⑵PCNA was negative in the medium and endothelium of sham-injured arteries.Positive cell rate of PCNA was gradually increased at 1～14 days in the medium and at 5～14 days in the neointima after injury,with the maximum rate at 14 days.However,it declined gradually after 28 days.Positive cell rate of PCNA in the neointima was slightly higher than that in the medium.⑶SM?-actin was positive in the medium,negative in the endothelium of sham-injured arteries.Positive cell area of SM?-actin initially decreased at 1 day in the medium after injury with the minimum rate at 3 days,but it increased gradually after 5 days.Expression of SM?-actin in the neointima was slightly less than that in the medium.⑷p38 expression was very low or negative in the medium of sham-injured arteries.Expression of p38 was sustained and increased at 1～35 days after injury with the most remarkable elevation at 3～14 days.Expression of p38 in the neointima was higher than that in the medium.There was positive relationship between the p38 expression and PCNA expression in the vascular wall at different time points after injury.Elevation of p38 was earlier than decrease of SM?-actin.Conclusion There was a close relationship between the phenotypic modulation and proliferating ability of VSMC.P38 participated in signal transduction of phenotypic modulation of VSMC after intimal injury.