Angiotensin II is known to stimulate angiogenesis in the peripheral circulation through activation of the AT₁ receptor. This study investigated the effect of selective angiotensin receptor blockade on cerebral cortical microvessel density. Rats (6-7 wks old, N=5-17) were instrumented with femoral arterial and venous indwelling catheters for arterial blood pressure measurement and drug administration. Rats were treated for 3 or 14 d with AT₁ receptor blocker losartan (50 mg/d in drinking water) or vehicle. Brains were sectioned, immunostained for CD31, and microvessel density was measured. Treatment with losartan for 3 d or 14 d (3d: 92 ± 1 mm Hg, 14 d: 99 ± 2 mmHg) resulted in a slight decrease in MAP compared to vehicle (109 ± 3 mm Hg, 125 ± 4 mm Hg). A furosemide + captopril 14 day treatment group (96 ± 3) was added to control for the blood pressure change. Microvessel density increased in groups treated with losartan for 14 days (429 ± 13) compared to vehicle (383 ± 11 vessels/mm²), and with losartan + PD123319 (467 ± 21), but did not change with furosemide + captopril (364 ± 7). Thus, AT₁ receptor blockade for 14 days resulted in increased cerebral microvessel density in a blood pressure-independent manner.