Salvia miltiorrhizaBunge is known to be effective for the treatment of cardiovascular diseases. Here, we have isolated tanshinone IIA (T-IIA) fromS. miltiorrhizaBunge. The aim of this study is to address the mechanisms where apolipoprotein B-100 (ApoB) regulation is associated with T-IIA, since T-IIA regulates the lipoprotein metabolism in liver cells. Human HepG2 cells treated with T-IIA for 24 h exerted a dose-dependent inhibitory effect on ApoB secretion together with triglyceride. However, another secretory protein, albumin, was unaffected by T-IIA treatment, indicating that the effect of T-IIA is specific for ApoB secretion. T-IIA decreased the transcription level of microsomal triglyceride transfer protein gene, suggesting that lipoprotein assembly is likely to be involved in the inhibited ApoB secretion. Interestingly, T-IIA inhibited ApoB secretion via a proteasome-dependent pathway. Our results suggest that T-IIA is an influential inhibitor of ApoB secretion and triglyceride secretion in liver cells. Copyright © 2008 John Wiley & Sons, Ltd.