Aims:　Transcription　is　a　crucial　step　for　human　immunodeficiency　virus　1　(HIV-1)　gene　expression　in　infected　host　cells.　The　HIV-1　Tat　activates　the　nuclear　factor-kappa　B　(NF-kappa　B)　signaling　transduction　pathway,　which　is　necessary　for　viral　replication.　Epigallocatechin-3-gallate　(EGCG)　has　antioxidant,　anti-inflammatory,　and　anti-viral　properties.　In　this　study,　we　investigated　the　effects　of　EGCG　on　Tat-induced　HIV-1　transactivation　and　potential　mechanisms　by　which　EGCG　inhibited　activation　of　NF-kappa　B　pathway.　Main　methods:　HeLa-CD4-long　terminal　repeat　(LTR)-beta-gal　(MAGI)　cells　were　transfected　with　Tat　plasmid.　Tat-induced　HIV-1　LTR　transactivation　was　determined　by　MAGI　cell　assay.　The　reactive　oxygen　species　(ROS)　levels　and　glutathione　(GSH)　levels　were　measured.　In　addition,　the　protein　expressions　were　assayed　by　western　blotting.　Key　findings:　Tat　caused　a　significant　decrease　in　the　intracellular　glutathione　(GSH)　levels,　a　mild　increase　in　the　expression　of　nuclear　levels　of　NF-E2-related　factor-2　(Nrf2),　a　significant　increase　in　the　levels　of　NF-kappa　B　(phosphorylation　of　p65　and　IKK)　and　a　significant　increase　in　ROS　production.　EGCG　supplementation　significantly　improved　the　changes　associated　with　Tat-induced　oxidative　stress　by　increasing　nuclear　levels　of　Nrf2,　decreasing　levels　of　NF-kappa　B　and　ROS　production.　EGCG　reversed　Tat-mediated　AKT　activation　and　AMPK　inhibition　in　MAGI　cells.　EGCG　inhibited　Tat-induced　LTR　transactivation　in　a　dose-dependent　manner.　Significance:　The　results　suggest　that　Nrf2　signaling　pathway　may　be　the　primary　target　for　prevention　of　Tat-induced　HIV-1　transactivation　by　EGCG,　and　EGCG　also　reduce　NF-kappa　B　activation　by　inhibiting　AKT　signaling　pathway　and　activating　AMPK　signaling　pathway.　(C)　2012　Elsevier　Inc.　All　rights　reserved.