The process of vascular remodeling is associated with increased hypoxia. However, the contribution of hypoxia-inducible factor 1 alpha (HIF1 alpha), the key transcription factor mediating cellular hypoxic responses, to vascular remodeling is established, but not completely understood. In the angiotensin II (Ang II)-induced vascular remodeling model, HIF1 alpha was increased and activated in vascular smooth muscle cells (VSMCs). Selective genetic disruption of Hif1 alpha in VSMCs markedly ameliorated Ang II-induced vascular remodeling, as revealed by decreased blood pressure, aortic thickness, collagen deposition, inflammation, and aortic stiffness. VSMC Hif1 alpha deficiency also specifically suppressed Ang II-induced infiltration of CD45(+)CD11b(+)F4/80(+)CD206(-) M1 macrophages into the vessel. Mechanistically, HIF1 alpha deficiency in VSMCs dramatically suppressed the expression of CCL7, a chemokine critical for macrophage recruitment. Bioinformatic analysis and chromatin immunoprecipitation assays revealed three functional hypoxia-response elements in the Ccl7 promoter, indicating that Ccl7 is a direct HIF1 alpha target gene. Blocking CCL7 with antibody in vivo alleviated Ang II-induced hypertension and vascular remodeling, coincident with decreased macrophage infiltration. This study provides direct evidence that HIF1 alpha activation in VSMCs exacerbates Ang II-induced macrophage infiltration and resultant vascular remodeling via its target gene Ccl7, and thus may serve as a potential therapeutic target for remodeling-related vascular disease.