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Background: This study directly and dynamically investigated the effects of SL extract (i.e., a combination of Radix Salviae miltiorrhizae and Andrographis paniculata extract) on plaque progression in vivo by high resolution ultrasound biomicroscopy (UBM). Methods: An atherosclerosis model was established by placing a perivascular collar on the right common carotid artery in apolipoprotein E-deficient (ApoE-/-) mice. Thickness, plaque area and local blood flow were observed by UBM, pathological changes were observed by histochemical staining, and lipid levels were measured by respective commercially available kits. Results: Compared with the model group, the SL extract groups showed reduced wall thickness of the aortic arch (GC: P = 0.001, P = 0.002, and P < 0.001; LC: P < 0.001, P < 0.001, and P < 0.001; BC: P = 0.027, P = 0.017, and P = 0.003; respectively), which presented with retarded plaque progression of the cartoid artery with concordantly increased blood flow (P = 0.002 and P < 0.001) as visualized in vivo by UBM. Histological analysis confirmed the reduction of carotid atherosclerosis. Conclusions: The SL extract inhibited the formation of atherosclerotic plaques in an ApoE-/- mice model by UBM analysis, and did so by effects that ameliorated local blood flow and improved blood lipid levels. [ABSTRACT FROM AUTHOR]