Intake of anthocyanin-rich foods has been associated with a reduced risk of cardiovascular diseases. Supplementation with anthocyanin-rich extracts from black rice or purple sweet potato was reported to attenuate atherosclerotic lesion development in apolipoprotein E-deficient (apo E(-/-)) mice. However, the mechanism(s) of their preventive action are not completely understood. Previous studies revealed that anthocyanins altered mRNA levels of genes related to atherosclerosis in cultured macrophages and endothelial cells, but in vivo studies remain scarce. The aim of the study was to investigate the impact of bilberry anthocyanin-rich extract (BE) supplementation on gene expression in the liver of apo E(-/-) mice, the widely used model of atherosclerosis. The liver was chosen because it is the main site of lipid metabolism. Apo E(-/-) mice received for 2 weeks a standard diet supplemented with a nutritional dose of BE (0.02%). This study focused on the early stage of atherosclerosis development for better assessment of anthocyanin action on initiation mechanisms of this pathology. The results showed that a 2-week supplementation significantly reduced plasmatic total cholesterol and hepatic triglyceride levels, whereas the plasmatic antioxidant status remained unchanged. Transcriptional analysis, using microarrays, revealed that the expression of 2,289 genes was significantly altered. BE over-expressed genes involved in bile acid synthesis and cholesterol uptake into the liver and down-regulated the expression of pro-inflammatory genes. These results suggest an anti-atherogenic effect of BE through the regulation of cholesterol metabolism and liver inflammation and provide a global integrated view of the mechanisms involved in the preventive action of this extract.