Toll-like receptors (TLRs) are pattern recognition receptors of the innate immune system that recognize endogenous damage-associated molecular patterns (DAMPS). TLR2 plays a role in cardiovascular diseases such as atherosclerosis and heart failure, but its role in hypertension is unknown. Angiotensin II (ANG), the effector molecule of the renin-angiotensin system, has been shown to cause an immune response leading to an inflammatory profile, in addition to its effects on vascular tone and sodium balance. We hypothesized that signaling through TLR2 in ANG-induced hypertension contributes to an increase in resistance artery contractility and vascular dysfunction. Sprague-Dawley rats were implanted with osmotic mini-pumps dispensing ANG (60 mg/day) for a 28 day period. Systolic blood pressure (measured directly via femoral canulation to confirm the ANG rats as a model of hypertension) was significantly increased in the ANG-treated rats (170 ±4.79 mmHg) vs. control (97 ±6.9 mmHg (p<0.05)). Concentration response curves to norepinephrine (NE; 10-9-10-4 M) were performed in second and third order mesenteric arteries from control and angiotensin-treated rats. Vessels were pre-incubated with and without antibody to TLR2 (1μg) for 35 minutes prior to the concentration-response curves to determine the impact of TLR2 blockade. The EMax (force of contraction as % of maximum KCl response) of the ANG vessels treated with anti-TLR2 was significantly lower than that of the ANG vessels alone (EMax: 129.2±10.69% vs 183.8±16.73%, respectively), and comparable to control-vessel levels (EMax in control vessels: 135.1±4.360%, p<0.05). Additionally, we sought to determine protein levels of TLR2 and downstream signaling protein MyD88 in the mesenteric arteries. In the arteries from the ANG treated animals, TLR2 expression was significantly increased 2.95±0.20 fold above control, and MyD88 expression was increased 1.35±0.06 fold above control (p<0.05). This suggests that TLR2 signaling leads to augmented contractility and is associated with the vascular dysfunction observed in hypertension.