Aim To investigate the effect of rapamycin on phenotype of VSMC and intimal hyperplasia in rat cardiac allograft. Methods Heterotopic heart transplantation models were established. The experimental rats were divided into four groups. Normal hearts of wistar rats served as controls. In isograft group,hearts from wistar rats were heterotopically transplanted to wistar rats with no immunosuppressant administraiton. In allograft group,hearts from wistar rats were heterotopically transplanted to SD rats. CyclosporineA group had Cyclosporine A,10 mg/(kg·d),administration subcutaneously. Rapamycin group had rapamycin,1.25 mg/(kg·d),administration by oral intubation after cardiac transplantation. All of the animals were killed at 60 day after transplantation. Phenotype of VSMC was observed with electron microscope. Coronary artery were analyzed for intimal area. Immunohistochemistry method was used for analysing the expression of VSM α-actin in the cardiac allograft. Results In normal hearts and isografts,the vascular intimal thickness were lower than those in the allografts. Compared with cyclosporine treated allografts,the vessel disease in Rapamycin treated allografts decreased significantly 60 days after transplantation (P><0.01). In normal hearts and isografts,VSMα-actin was only localized in media. Electron microscope showed VSMC were contractile. VSMα-actin was found in the proliferative vascular intimal in Cyclosporine A treated allografts and electron micro scope showed most of VSMC changed from contractile to synthetic. It was abundant in the proliferative vascular intimal 60 days after transplantation in Cyclosporine A treated allografts while decreased in Rapamycin treated allografts and electron microscope showed the morphologic characteristic of VSMC changed from synthetic to contractile. Conclusion Rapamycin can influence the phenotype transform of VSMC,and reduce the degree of neointimal hyperplasia of transplanted cardiac in rat.