Cerebral venous hypertension (VH) and angiogenesis are implicated in the pathogenesis of brainarteriovenous malformation and dural arteriovenous fistulae. We studied the association of VH andangiogenesis using a mouse brain VH model. Sixty mice underwent external jugular vein andcommon carotid artery (CCA) anastomosis (VH model), CCA ligation, or sham dissection (n = 20).Hypoxia-inducible factor-1a (HIF-1a), vascular endothelial growth factor (VEGF) and stromal-cellderivedfactor-1a (SDF-1a) expression, and matrix metalloproteinase (MMP) activity were analyzed.We found VH animals had higher (P< 0.05) sagittal sinus pressure (8±1mmHg) than control groups(1±1mmHg). Surface cerebral blood flow and mean arterial pressure did not change. Hypoxiainduciblefactor-1a, VEGF, and SDF-1a expression increased (P < 0.05). Neutrophils and MMP-9activity increased 10-fold 1 day after surgery, gradually decreased afterward, and returned tobaseline 2 weeks after surgery. Macrophages began to increase 3 days after surgery (P< 0.05), whichcoincided with the changes in SDF-1a expression. Capillary density in the parasagittal cortexincreased 17% compared with the controls. Our findings suggest that mild nonischemic VH resultsin a pro-angiogenic stage in the brain by upregulating HIF-1 and its downstream targets, VEGF andSDF-1a, increasing leukocyte infiltration and MMP-9 activity.