Objective TanshinoneⅡ-A(Tan),a bioactive diterpene isolated fromSalvia miltiorrhiza Bunge(Danshen),possesses anti-oxidant and anti-in-flammatory activities.The present study investigated whether Tan can reduce and stabilize atherosclerotic plaques in Apolipoprotein E knockout(ApoE-/-) mice maintained on a high cholesterol diet(HCD).Methods and Results Six week-old mice challenged with HCD were ran-domly assigned to 4 groups: C57BL/6J,ApoE-/-,ApoE-/-+30 mg/kg.d Tan and ApoE-/-+10 mg/kg.d Tan.After 16 weeks of inter-vention,Tan treated mice showed decreased atherosclerotic lesion size in the aortic sinus and face aorta.Furthermore,immunohistochemical a-nalysis revealed that Tan rendered the lesion composition a more stable phenotype as evidenced by reduced necrotic cores,decreased macrophageinfiltration,increased smooth muscle cell and collagen content.Tan also significantly reduced in situ superoxide anion production,aortic expres-sion of NF-κB,and matrix metalloproteinase-9(MMP-9).In vitro treatment of RAW264.7 macrophages with Tan significantly suppressed oxi-dized LDL-induced reactive oxygen species production,pro-inflammatory cytokine(IL-6,TNF-α,MCP-1) expression,and MMP-9 activity.Conclusions Tan attenuates the development of atherosclerotic lesions and promotes plaque stability in ApoE-/-mice by reducing vascular oxi-dative stress and inflammatory responses.Our findings highlightTan as a potential therapeutic agentto preventatherosclerotic cardiovascular dis-eases. Objective Tanshinone II-A (Tan), a bioactive diterpene isolated from Salvia miltiorrhiza Bunge (Danshen), possesses anti-oxidant and anti-in-flammatory activities. The present study investigating whether Tan can reduce and stabilize atherosclerotic plaques in Apolipoprotein E knockout (ApoE- / -) mice maintained on a high cholesterol diet (HCD). Methods and Results Six week-old mice challenged with HCD were ran-domly assigned to 4 groups: C57BL / 6J, ApoE - / - / kg.d Tan and ApoE - / - + 10 mg / kg.dTan.After 16 weeks of inter -vention, Tan treated mice showed decreased atherosclerotic lesion size in the aortic sinus and face aorta. Fusionrther, immunohistochemical a-nalysis revealed that Tan rendered the lesion composition a more stable phenotype as evidenced by reduced necrotic cores, decreased macrophage infiltration, increased smooth muscle cell and collagen content. Tan also significantly reduced in situ superoxide anion production, aortic expres-sion of NF-κB, and matrix metalloproteinase -9 (MMP-9) .I n vitro treatment of RAW264.7 macrophages with Tan significantly suppressed oxi- dized LDL-induced reactive oxygen species production, pro-inflammatory cytokine (IL-6, TNF- [alpha], MCP- attenuates the development of atherosclerotic lesions and promotes plaque stability in ApoE - / - mice by reducing vascular oxi-dative stress and inflammatory responses. Our findings highlightTan as a potential therapeutic agent to preventatherosclerotic cardiovascular dis-eases.