Abstract： Background The results of clinical trials of rapamycin-eluting stents reduce restenosis have been quite promising. The main purpose of this study was to characterize the in vivo pharmacokinetics of high dose rapamycin (Rapa)-eluting stents in a miniswine coronary model.Methods Ten miniswines underwent placement of 18 high dose Rapa-eluting stents in the left anterior descending and right coronary arteries. At the planned times of the 1.5th, 12th, 24th hour, 3th, 7th and 28th day, the animals (n=1, 1, 2, 2, 2, and 2, respectively) were euthanized after completion of coronary angiography. Blood samples were obtained at 0, 10, 20, 30 minutes; 1, 2, 6, 24 hours; and 3, 7, 28 days to determine systemic Rapa levels. Rapa levels in whole blood, arterial wall, heart, renal and liver tissues were determined by high-performance liquid chromatography/mass spectroscopy.Results Peak whole blood concentration (Cmax), time to peak concentration (tmax), elimination half-life (t1/2β), area under the curve (AUC), and apparent systemic clearance (Cl/F) were (10.91±1.28) ng/ml, (2.0±0.2) hours, (7.25±0.63) hours, (1.15±0.11) ng·h·ml-1, and (180±12) ml·h-1·kg-1, respectively. More than 95% Rapa detected is localized in the coronary artery surrounding the stent and heart.Conclusion Stent-based delivery of Rapa via a copolymer stent is feasible and safe. This strategy holds promise for the prevention of stent restenosis.