Hypertensive encephalopathy occurs when acute changes in blood pressure cause breakdown of the blood—brain barrier (BBB). Angiotensin II (Ang II) plays a role in this pathophysiology. We determined whether Ang II directly regulates endothelial cell function at the BBB. In BBB microvessel endothelial cells (MECs), the Ang II (100 nmol/L; 0 to 6 h) effects on permeability to ¹²⁵I-albumin and transendothelial electrical resistance (TEER) were assessed. Angiotensin II (100 nmol/L) caused significant time-dependent changes in both ¹²⁵I-albumin permeability (25%) at 2 h and TEER (−8.87 Ω·cm²) at 6 h. Next, MECs were pretreated with the Ang II type 1 (AT₁) receptor blocker telmisartan (1 μmol/L) or the Ang II type 2 (AT₂) receptor blocker PD123,319 (1 μmol/L) followed by treatment with Ang II (100 nm). Telmisartan completely inhibited the Ang II-induced increase in ¹²⁵I-albumin permeability in MECs whereas PD123,319 had no effect. Using western blot analysis, we showed that MECs express AT₁ receptors but not AT₂ receptors. Treatment with Ang II (100 nmol/L; 0 to 6 h) also increased total protein kinase C activity. In contrast, Ang II had no effect on the expression of occludin, claudin 5, or actin. These results show that Ang II directly modulates transcytotic and paracellular permeability in BBB endothelial cells and could contribute to the pathophysiology of hypertensive encephalopathy.