Abstract —The predominant cause of restenosis after angioplasty is now thought to be inward remodeling, but the mechanisms responsible are unknown. Remodeling in normal vessels is regulated by the endothelium in response to altered shear stress. Although the endothelium is often damaged by angioplasty, restenosis rates after angioplasty have been correlated with impaired coronary flow. Thus, we examined how increases or decreases in blood flow through balloon catheter–injured rat carotid arteries affect vessel morphometry (4, 10, and 28 days), cell migration (4 days), and levels of promigratory mRNAs (2 and 10 days). After 28 days, the luminal area in vessels with low blood flow was significantly less than in those with normal and high blood flow (0.17±0.01 [low] versus 0.24±0.06 [normal] versus 0.30±0.02 [high] mm ² , P <0.01), predominantly because of accentuated inward remodeling (or reduced area within the external elastic lamina; 0.42±0.02 [low] versus 0.54±0.07 [normal] versus 0.53±0.04 [high] mm ² , P <0.05). Low flow also enhanced smooth muscle cell migration 4 days after injury by 90% above normal and high flows ( P <0.01). Two days after injury, low flow significantly increased levels of mRNAs encoding promigratory peptides (integrin α _v β ₃ , transforming growth factor-β ₁ , CD44v6, MDC9, urokinase plasminogen activator receptor, and β-inducible gene h3); these changes persisted 10 days after injury and were localized to the neointima. Low blood flow may promote restenosis after angioplasty because of its adverse effect on vessel remodeling, and it is associated with the augmented expression of multiple genes central to cell migration and restenosis.