Hypolipidemic effects of Agastache rugosa essential oil (AREO) were investigated. Gas chromatographymass spectrometry (GC-MS) analysis showed that the major compound in AREO is limonene (47%, w/w). AREO (1 mg/mL) markedly reduced low density lipoprotein (LDL) oxidation (-93%). After 3-week feeding of AREO, plasma cholesterol (-28%) and triglyceride levels (-26%) were significantly decreased in C57BL/6J mice. Mouse hepatic transcriptome profiling with oligonucleotide microarray revealed that AREO altered the expression of 2,524 genes. Notably, significant reductions in sterol regulatory element binding factor (SREBF)-1 and SREBF-2 mRNA levels were detected. Protein expression of HMG-CoA reductase, a major target for SREBP-2, was reduced in HepG2 cells (-36%) and in mouse liver (-35 %). AREO also significantly increased mRNA (+40%) and protein (+83%) expression of the LDL receptor in HepG2 cells and mouse liver, respectively. Our findings suggest that AREO may prevent atherosclerosis via the inhibition of LDL oxidation, down-regulation of SREBF-2 and HMG-CoA reductase expression, and up-regulation of LDL receptor expression.