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Leaf extract of Ginkgo biloba (GBE) is increasingly used as a herbal medicine for the treatment of neurodegenerative, cardiovascular and cerebrovascular diseases. Several studies have demonstrated many protective effects of GBE in neurons, the endothelium and liver. In this study, we investigated the molecular mechanisms underlying the effects of GBE in disorders induced by long-term exposure to a high-fat diet (HFD). Rats were fed an HFD with or without the GBE product GBE50 for 19 weeks. We found that GBE50 reduced the development of fatty liver induced by an HFD and inhibited the commonly observed elevation of serum cholesterol and lactate dehydrogenase levels. Transcriptome profiling analysis showed that several genes were modulated by GBE50 in liver, including those involved in lipid metabolism, carbohydrate metabolism, vascular constriction, ion transportation, neuronal systems and drug metabolism. Notably, a number of genes coding for proteins involved in cholesterol metabolism were repressed, and some were upregulated. Fatty acid biosynthesis appeared to be repressed, whereas fatty acid metabolism appeared to be enhanced. In conclusion, using transcriptome profiling analysis, we demonstrated the molecular basis for the pleiotropic effects of GBE50, particularly those involved in lipid metabolism. This study provided new clues for further pharmacological study of GBEs. [ABSTRACT FROM AUTHOR]