Female lean Zucker rats were fed for four weeks with either a control diet or the same diet enriched with 2% (w/w) cholesterol and cholic acid (0.5%, w/w). This treatment resulted in a 6-fold increase in plasma total cholesterol. A 30% decrease was observed in plasma post-heparin HL activity, in contrast with lipoprotein lipase, which was unmodified in the cholesterol/cholate-fed rats. HL activity measured in liver homogenate from these rats was also decreased (-30%, p < 0.05), as was its protein mass, quantified by immunoblot analysis (-57%, (p < 0.01), whereas HL mRNA levels were 3-fold lower in the cholesterol/cholate-fed rats. We conclude that the cholesterol/cholate-enriched diet decreases the HL gene expression by acting at the transcriptional level and/or by affecting HL mRNA stability, or both.