Background: Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific mitogen, which enhances vascular permeability and stimulates angiogenesis. However, it is not known whether anti-peptides can reduce neointima formation in cases of vascular injury. This study was undertaken to test the hypothesis that the neointima hyperplasia induced by balloon injury is inhibited by blocking VEGF and VEGF receptor-1 (VEGFR-1) with anti-VEGF peptides. Methods: An antipeptide against VEGF (dRK6) and anti-flt-1 against for VEGFR-1(anti-flt-1) were synthesized at the Pohang University of Science and Technology in Korea. Male Sprague-Dawley rats weighing 300-350 g, were subcutaneously injected 0.5 g/kg of dRK6 or 0.5 g/kg of anti-flt-1, which were dissolved in phosphate buffer solution 2 days before carotid balloon-injury and then injected daily for 2 weeks after carotid balloon injury. Results: Neointima formation was suppressed in both the dRK6 and anti-flt-1 groups versus untreated controls at 2 weeks after carotid balloon-injury (neointima area ; control group 0.44 짹 0.09 ���, dRK6 group 0.25 짹 0.05 ���, anti-flt-1 group 0.19 짹 0.05 ���, P<0.01). Anti-flt-1 peptide and dRK6 reduced the number of proliferative BrdU-labeled cells in the neointima (BrDU (+) cell ; control group 16.4 짹 10.6%, dRK6 group 3.7 짹 2.1%, anti-flt-1 group 5.9 짹 3.4%, P<0.05). The staining for VEGF and VEGFR-1 was increased in the neointima of controls after balloon injury, but dRK6 and anti-flt-1 inhibited VEGFR-1 expression. In addition, inflammatory response, as determinded by monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL-6) upregulation, which was evident in controls, was inhibited by both dRK6 and anti-flt-1. Conclusions: Anti-vascular endothelial growth factor peptides reduced the inflammation and neointima formation in balloon injured rat carotid arteries.