Objectives: The present study was designed to evaluate and compare endothelial function and vascular biological responses following implantation of a novel, non-polymeric cerivastatin-eluting stent (CES) versus polymer-based paclitaxel-eluting stent (PES) in a rabbit iliac artery model. Methods : In vitro, human aortic and coronary smooth muscle cells (hASMC & hCSMC), as well as aortic and coronary endothelial cells (hAEC & hCEC), were cultured; and IC50 curves were determined for cerivastatin (CER). In vivo PES (n=6), CES (n=12), and polymer-free sol-gel only (sol-gel, n=12) stents were implanted in 15 rabbits. Vasomotor function was investigated at 28 days by infusion of acetylcholine (Ach) and nitroglycerin (NTG). Animals were terminated for histopathological analyses. Results: CER was cytotoxic to hASMC and hCSMC (IC50s of 10 −6 M and 10 −5 M, respectively), although such cytotoxic effects were not observed for hAEC and hCEC at maximal study dose. PES-associated vasodilation response to endothelial-dependent Ach was significantly suppressed at both proximal and distal adjacent arterial segments, as compared to CES and sol-gel. Furthermore, microscopically, the percent area stenosis was higher for PES (25±3%) compared to both CES and sol-gel (15±6% and 16±7%, p < 0.05, respectively). Medial area was lower for PES (0.3±0.04 mm 2 ) than CES and sol-gel (0.5±0.03 and 0.4±0.04 mm 2 , p <0.001, respectively). Additionally, re-endothelialization scores were comparable among groups ( P =NS); but profound fibrin deposition was clearly evidenced in PES ( p < 0.05 vs. others). Conclusions: CER elicits a differential effect on hSMC compared to hEC in vitro. In contrast to PES, a novel bioabsorbable sol-gel coated CES demonstrated superior neointimal inhibition and less vessel toxicity, as well as preservation of vasomotor function in the rabbit iliac model.