Exercise　training　is　one　of　the　major　non-pharmacological　treatments　for　hypertension.　However,　the　central　mechanism　by　which　exercise　training　attenuates　the　hypertensive　responses　remains　unclear.　Irisin　is　a　muscle-secreted　cytokine　derived　from　fibronectin　type　III　domain　containing　5　(FNDC5)　that　will　be　released　into　the　circulation　during　exercise.　We　hypothesized　that　irisin　may　play　a　role　in　the　blood　pressure　regulation　by　exercise.　To　examine　the　hypothesis,　our　study　investigated　the　effect　of　irisin　on　hypertension　and　its　central　mechanism.　The　study　was　performed　in　spontaneously　hypertensive　rats　(SHRs)　and　normotensive　Wistar-Kyoto　rats.　We　found　that　intravenous　injection　of　irisin　effectively　reduced　blood　pressure,　plasma　norepinephrine,　paraventricular　nucleus　(PVN)　levels　of　neuronal　activation,　oxidative　stress　and　inflammation　in　SHRs.　Moreover,　irisin　activated　nuclear　factor　E2-related　factor-2　(Nrf2)　and　restored　the　imbalance　of　neurotransmitters　in　the　PVN.　Our　study　also　found　PVN　knockdown　of　Nrf2　abolished　the　protective　effects　of　irisin　on　hypertension.　These　findings　demonstrate　irisin　can　improve　hypertension　via　Nrf2-mediated　antioxidant　in　the　PVN.