Abstract: AIM: To investigate the effect of tanshinone IIA on adiponectin biosynthesis. METHODS: The differentiation state of 3T3-L1 adipocytes was checked by Oil Red O staining. mRNA levels were examined by real-time PCR. Adiponectin oligomers were subjected to 2%15% gradient SDS-PAGE and then detected using western blotting. Gene silencing experiments were performed using standard siRNA methods. RESULTS: It was found that tanshinone IIA, a diterpenoid naphthoquinone from the Chinese traditional herb Danshen (Salvia miltiorrhiza), inhibited the differentiation of preadipocytes and down-regulated the expression of adiponectin. In contrast, tanshinone IIA promoted the assembly of high-molecular weight (HMW) adiponectin during differentiation and in mature adipocytes. Tanshinone IIA activated AMP-activated protein kinase (AMPK) in 3T3-L1 adipocytes, and suppression of the AMPK pathway blocked the effect of tanshinone IIA on adiponectin expression and multimerization. CONCLUSION: These data suggest that tanshinone IIA promotes the assembly of HMW adiponectin through a process involving AMPK activation.