Royal jelly (RJ) has various pharmacological actions, including hypolipidaemic, hypocholesterolaemic and anti-atherosclerotic effects, in experimental animals but the molecular mechanisms involved remain unclear. Here, we investigated changes in the expression of lipid metabolism-associated genes in the liver of RJ-treated mice by means of a DNA microarray technique to obtain clues to the mechanism of the hypocholesterolaemic action of RJ. We compared the hepatic gene expression profiles in three groups of mice fed a diet containing 5% RJ, a diet containing 5% RJ stored at 40°C for 7 days (40-7d RJ) or a control diet which provided the same total energy as the other diets. RJ decreased gene expression of squalene epoxidase (SQLE), which is a key enzyme in cholesterol biosynthesis, and sterol regulatory element-binding protein (SREB)-1, which may be a transcriptional factor of SQLE. It increased gene expression of low-density lipoprotein receptor (LDLR), which is involved in cholesterol incorporation in liver. Thus, the hypocholesterolaemic action of RJ appears to be associated with a decrease of SQLE and an increase of LDLR in mice.