Aim To investigate the effect of rapamycin on phenotype of vascular smooth muscle cell(VSMC) and intimal hyperplasia in a rat model of restenosis post balloon injury. Methods Twenty-six healthy adult male rats were randomly divided into four groups: sham group (n=2), balloon group (n=8): received balloon injury only, cellulose group(n=8) received the vehicle solution, and rapamycin group(n=8) intramusclar administration of rapamycin (suspended in solution containing 0.2% sodium carboxymethyl cellulose) started 3 days before injury at a dose of 0.5 mg/kg and continued for 14 days at a dose of 0.25 mg/kg. Phenotype of VSMC was observed with electron microscope. Abdominal aortas were analyzed for intimal area, mean intimal thickness, media area and intimal/media area ratio. Results Electron microscope showed the morphilogic characteristics of VSMC changed from contractile to synthetic after balloon injury. VSMC showed less organelles and more myofilament when exposed to rapamycin. Neointimal area and intimal/media area ratio 14 days after injury showed a 36.4% and 28.9% reduce in the animals receiving rapamycin compared with those receiving cellulose respectively(0.14±0.03 mm 2 vs 0.23 ±0.06 mm 2 and 17.70%±3.37% vs 28.86%±10.25%, respectively, p<0.01). Conclusion Rapamycin can influence the phenotype transform of VSMC, and reduce the degree of neointimal hyperplasia.