Endothelium plays an important role in vascular smooth muscle cell proliferation and thrombus deposition. We thus hypothesized that local delivery of recombinant human vascular endothelial growth factor (rhVEGF) might reduce in-stent intimal formation. Balloon injury followed by Palmaz-Schatz stent implantation was performed in the external iliac artery of 30 New Zealand rabbits. Animals were then randomized to: 1) no local delivery (Control group, n=10); 2) local delivery via a channel balloon catheter of 100 microg rhVEGF165 (VEGF group, n=10); or 3) local delivery of the vehicle solution (Vehicle group, n=10). Animals were sacrificed 28 days later and morphometric analysis was performed. Maximal intimal area was reduced from 1.47+/-0.12 mm2 and 1.44+/-0.10 mm2 in the Control and Vehicle groups, respectively, to 0.87+/-0.06 mm2 in the VEGF group (p<.001). Accelerated endothelialization by local delivery of an endothelial-specific growth factor, rhVEGF, significantly reduces in-stent intimal formation and could constitute an attractive alternative to direct antiproliferative strategies.