Angiotensin　II　(Ang　II)　is　a　vasoactive　peptide　that　elevates　arterial　blood　pressure　and　leads　to　hypertension.　Ang　II　has　been　reported　to　induce　endothelial　dysfunction　by　induction　of　apoptosis　and　oxidative　stress　in　vascular　endothelial　cells.　Sirtuin6　(SIRT6)　has　emerged　as　a　critical　regulator　for　modulating　Ang　II-induced　injury　of　the　cardiovascular　system.　However,　little　is　known　about　the　role　of　SIRT6　in　regulating　Ang　II-induced　injury　in　vascular　endothelial　cells.　Here,　our　results　showed　that　SIRT6　expression　was　decreased　in　vascular　endothelial　cells　exposed　to　Ang　II.　This　was　accompanied　by　decreased　cell　viabilities　as　well　as　increased　apoptosis　and　the　production　of　reactive　oxygen　species.　Functional　experiments　showed　that　the　overexpression　of　SIRT6　significantly　prohibited　Ang　II-induced　apoptosis　and　reactive　oxygen　species　generation,　while　silencing　SIRT6　resulted　in　the　opposite　effect.　Notably,　our　results　showed　that　overexpression　of　SIRT6　resulted　in　a　significant　increase　in　the　nuclear　expression　of　nuclear　factor　erythroid　2-related　factor　2　(Nrf2)　and　upregulated　the　expression　of　the　Nrf2　target　gene　in　vascular　endothelial　cells　exposed　to　Ang　II.　Moreover,　knockdown　of　Nrf2　significantly　blocked　the　SIRT6-mediated　protection　effect　against　Ang　II-induced　apoptosis　and　reactive　oxygen　species　generation.　Taken　together,　these　results　demonstrate　that　SIRT6　overexpression　alleviates　Ang　II-induced　apoptosis　and　oxidative　stress　in　vascular　endothelial　cells　by　promoting　Nrf2　antioxidant　signaling.　Our　study　suggests　that　SIRT6　may　serve　as　a　potential　therapeutic　target　for　treating　hypertension　associated　with　endothelial　dysfunction.