The novel finding of the present study are that: (i) The TLR4/MyD88/NF-κB signaling was activated in the PVN in 2K1C renovascular hypertensive rats, and microinjection of TAK242 into the PVN inhibited TLR4/MyD88/NF-κB signaling and attenuated SBP; (ii) 8 weeks of aerobic exercise training significantly down-regulated TLR4/MyD88/NF-κB signaling transduction, down-regulated TNF-α and IL-1β protein expression in the PVN, reduced RSNA, and attenuated hypertensive response of 2K1C hypertensive rats. Here, TLR4 is linked to renovascular hypertension.