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Aim: To investigate the protective effect and the possible mechanism of curcumin on anti-atherosclerosis. Methods: Morphological changes of atherosclerotic le-sions taken from apoE knockout (apoE-/-) mice were determined by hematoxylin-eosin staining. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC. The protein expression of caveolin-1 was quantified by West-e blotting. Translocation and the expression of sterol response element-bind-ing protein-1 (SREBP-1) were indirectly detected by an immunofluorescence analysis. Results: The administration of 20 mg.kg-1.d-1 curcumin to apoE-/1 mice for 4 months induced a 50% reduction of atherosclerotic lesions and yielded a 5-fold increase in the caveolin-1 expression level as compared to the model group. Rat vascular smooth muscle cells (VSMC) pretreated with 50 mg.L-1 ox-lipid den-sity lipoprotein(ox-LDL) for 48 h increased cellular lipid contents, and stimulated SREBP-1 translocation, but decreased the caveolin-1 expression level. Lipid-loaded cells exposed to curcumin at various concentrations (12.5, 25, and 50 μmol.L-1) for different durations (0, 6, 12, 24, and 48 h) significantly diminished the number and area of cellular lipid droplets, total cholesterol, cholesterol ester, and free choles-terol accompanying the elevation of the caveolin-1 expression level (approximately 3-fold); the translocation of SREBP-1 from the cytoplasm to the nucleus was inhibited compared with the models. Lipid-loaded VSMC exposed to N-acetyl-Leu-Leu-norleucinal, a SREBP-1 protease inhibitor, showed increased nuclear trans-location of SREBP-1, reduced caveolin-1 expression level, and upregulated cellu-lar lipid levels. Conclusion: Curcumin inhibits ox-LDL-induced cholesterol accu-mulation in cultured VSMC through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP-1.