We investigated the role played by bradykinin 2 (B2) receptors in the exaggerated exercise pressor reflex in rats with a femoral artery ligated for 72hrs to induce simulated peripheral artery disease (PAD). We hypothesized that in decerebrate, unanesthetized rats with a ligated femoral artery, hindlimb arterial injection of HOE-140 (100ng, B2 receptor antagonist) would reduce the pressor response to 30s of electrically-induced 1 Hz hindlimb skeletal muscle contraction, and 30s of 1 Hz hindlimb skeletal muscle stretch (a model of mechanoreflex activation isolated from contraction-induced metabolite production). We hypothesized no effect of HOE-140 in sham-operated "freely perfused" rats. In both freely perfused (n=4) and "ligated" (n=4) rats, we first confirmed efficacious B2 receptor blockade by demonstrating that HOE-140 injection significantly reduced (P<0.05) the peak increase in mean arterial pressure (peak ΔMAP) in response to hindlimb arterial injection of bradykinin. In subsequent experiments, we found that HOE-140 reduced the peak ΔMAP response to muscle contraction in ligated (n=14; control: 23±2; HOE-140: 17±2 mmHg; P=0.03) but not freely perfused rats (n=7; control: 17±3; HOE-140: 18±4mmHg; P=0.65). Furthermore, HOE-140 had no effect on the peak ΔMAP response to stretch in ligated rats (n=14; control: 37±4; HOE-140: 32±5mmHg; P=0.13) but reduced the integrated area under the blood pressure signal over the final ~20s of the maneuver. The data suggest that B2 receptors contribute to the exaggerated exercise pressor reflex in rats with simulated PAD, and that contribution includes a modest role in the chronic sensitization of the mechanically-activated channels/afferents that underlie mechanoreflex activation.