The primary purpose of this investigation was to determine the role played by endoperoxide 4 receptors (EP4-R) and thromboxane A receptors (TxA-R) during isolated dynamic muscle mechanoreflex activation in rats with heart failure with reduced ejection fraction (HF-rEF) and sham-operated healthy controls. We found that injection of the EP4-R antagonist L-161,982 (1 μg) into the arterial supply of the hindlimb had no effect on the peak pressor response to dynamic hindlimb muscle stretch in HF-rEF (n = 6, peak ∆MAP pre: 27 ± 7; post: 27 ± 4 mm Hg; P = 0.99) or sham (n = 6, peak ∆MAP pre: 15 ± 3; post: 13 ± 3 mm Hg; P = 0.67) rats. In contrast, injection of the TxA-R antagonist daltroban (80 μg) into the arterial supply of the hindlimb reduced the pressor response to dynamic hindlimb muscle stretch in HF-rEF (n = 11, peak ∆MAP pre: 28 ± 4; post: 16 ± 2 mm Hg; P = 0.02) but not sham (n = 8, peak ∆MAP pre: 17 ± 3; post: 16 ± 3; P = 0.84) rats. Our data suggest that TxA-Rs on thin fibre muscle afferents contribute to the exaggerated mechanoreflex in HF-rEF.