Tanshinone　IIA　is　the　major　antioxidant　component　in　the　traditional　Chinese　medicine　Salvia　miltiorrhiza.　Transcription　factor　nuclear-factor-E2-related　factor　(Nrf2)　regulates　a　battery　of　antioxidant　response　element　(ARE)-regulated　genes.　The　aim　of　this　study　was　to　determine　the　effect　of　tanshinone　IIA　on　Nrf2　activation　and　intracellular　redox　status　in　human　aortic　smooth　muscle　cells.　Tanshinone　IIA　potentiated　tumor　necrosis　factor　U　(TNF-alpha)-mediated　nuclear　accumulation　of　Nrf2　and　expression　of　ARE-related　genes,　while　it　reversed　TNF-alpha-induced　down-regulation　of　intracellular　glutathione　(GSH),　NADPH　and　glucose　G-phosphate　dehydrogenase　(G6PDH)　levels.　Specific　silence　of　Nrf2　by　siRNA　down-regulated　tanshinone　IIA-induced　Nrf2　activation　and　increased　of　intracellular　GSH,　NADPH　and　G6PDH　levels.　Tanshinone　IIA-induced　Nrf2　activation　was　association　with　activation　of　ERK　and　PKB,　which　was　prevented　by　treatment　with　PD098059　or　wortmannin.　Tanshinone　IIA　attenuated　TNF-alpha,　angiotensin　II,　H2O2-mediated　reactive　oxygen　species　(ROS)　production.　These　results　demonstrated　that　tanshinone　IIA-induced　Nrf2　activation　is　the　major　regulatory　pathway　of　cytoprotective　gene　expression　against　oxidative　stress　via　ERK　and　PKB　signaling　pathways.　(c)　2007　Published　by　Elsevier　Inc.