BACKGROUND Panax notoginseng saponins (PNS) are ingredients extracted from traditional Chinese medicinal herb Panax notoginseng. It has been demonstrated that PNS have extensive effects on the cardiovascular system, including inhibition of platelet aggregation, increasing blood flow, improving left ventricular diastolic function in hypertensive patients and anti-inflammatory effect. OBJECTIVE Recent researches indicated that PNS administration inhibited foam cells' formation. The present study was designed to study the effects of PNS on atherogenesis and to explore the relevant molecular mechanisms. METHODS The Zymosan A induced atherosclerosis models were used to investigate the anti-atherosclerosis effects of PNS. The integrin express array was used to check the changes of integrins. The foam cell formation was observed with transmission electron microscope. The effect of PNS on phosphorylation of FAK on threonine 397 and protein level of NF-κB was also evaluated in vitro. RESULTS PNS treated rats had less plaque spots on the aortas compared with Zym induced group. The formation of foam cell was inhibited by PNS. Compared with Zym treated group, the expression of most integrin families decreased except Itgav and Itgb2 after PNS treatment. PNS inhibited phosphorylation of FAK on threonine 397 and translocation of NF-κB. CONCLUSIONS High fat diet together with Zym induces atherogenesis of rat. PNS inhibits zymosan A induced atherogenesis by suppressing FAK phosphorylation, integrins expression and NF-κB translocation.