Objective To investigate the inhibitory effect of astragaloside III（ASIII） on TNFR1-mediated signaling pathways in mouse arterial smooth muscle cells（ASMCs） and provide experimental evidence for the anti-inflammatory and anti-atherosclerotic actions of Chinese herbal medicine Radix Astragali（Huangqi）. Methods The effect of ASIII on the cell viability of ASMCs was evaluated by conducting a WST-1 assay. The mRNA levels of ICAM-1（intercellular adhesion molecule-1）， Lox-1（lectin-like oxidized LDL receptor-1） and ABCA1（ATP-binding cassette transporter A1） in ASMCs were measured using quantitative RT-PCR technique. Western Blot was performed to detect the effect of ASIII on TNF-α-induced modulation of ICAM-1， Lox-1 and ABCA1 protein levels. TNFR1-mediated phosphorylation and degradation of I Bα， and phosphorylation of AKT， ERKs and p38 were also measured by using Western Blot analysis. Results （1） ASIII， when used at a concentration between 30 nM and 10 μM， did not reduce the cell viability of ASMCs； （2） The TNFα-stimulated up-regulation of ICAM-1 and Lox-1， and down-regulation of ABCA1 expression level were inhibited by ASIII in a concentration-dependent manner； （3） ASIII suppressed the TNFR1-mediated phosphorylation and degradation of IκBα protein； （4） ASIII suppressed TNFR1-mediated phosphorylation of AKT， ERKs and p38. Conclusion ASIII inhibits the TNFR1-mediated intracellular signaling pathways in ASMCs， which may in part explain its anti-inflammatory and anti-antherosclerostic effects.