Angiotensin II (AII) has been shown to promote proliferation of vascular smooth muscle cells and inflammation, particularly after vascular injury, suggesting a role in restenosis. Numerous restenosis animal studies have successfully demonstrated reduced neointima formation with administration of high dose angiotensin converting enzyme (ACE) inhibitors. Recent human trials of ACE inhibitors on restenosis have failed to show such effects. It has been speculated that the negative outcomes of these studies were due to suboptimal dosing secondary to concerns for side effects. Drug-coated stents allow for high dose local drug delivery with minimal systemic effects. We hypothesized that local inhibition of ACE by stent-based controlled release of perindopril limits injury-induced neointima formation and inflammation in a rabbit balloon injury model. Channeled stents embedded with microspheres containing perindopril (released at 2mg per day over 28 days) or polymer only were deployed in the aortas of New Zealand White rabbits for 7 and 28 days. Stented aortas were subsequently subjected to balloon injury. The rabbits were fed a high cholesterol diet until sacrifice. Arteries receiving perindopril stents demonstrated decreased neointima formation and inflammation. The intima to media ratio was significantly less in the perindopril treated group versus control at day 7 (0.12 ± 0.02 vs. 0.20 ± 0.02, p=0.0001) and at day 28 (1.04 ± 0.06 vs. 1.42 ± 0.05, p=0.01). At day 7, the number of neutrophils in the intima per mm² was also significantly less in the perindopril treated group versus control (28.7 ± 3.95 vs. 66.5 ± 8.17, p=0.002). In conclusion, in a rabbit balloon injury model, local and controlled release of high dose perindopril using microsphere-embedded stents reduces neointima formation and inflammation. Use of stent-based ACE inhibitor delivery may allow for effective suppression of ACE and AII activity in future human trials.