Abstract: OBJECTIVE To explore the effects of Andrographolide on expression of SREBPs and lipid metabolism in HepG2 cells， and to study the possible mechanism. METHODS Cell viability was evaluated by Cell Counting Kit-8; Dual luciferase reporter gene assay was used to test the transcription activity of SREBP; The SREBPs target genes expressions were measured by Quantitative Real-Time PCR; The intracellular triglyceride (TG) and total cholestero l(TC) contents were measured by using commercially available test kits. RESULTS Andrographolide in 0~80 μmol/L concentration range has no effect on HepG2 cell activity; Andrographolide could markly inhibited human SRE promoter activity in a dose-dependent manner， and the mRNA level of SREBPs target genes were significantly downregulated by Andrographolide at the dose of 35 μmol/L. In addition， contents of intracellular cholesterol and triglyceride were significantly suppressed by Andrographolide treatment. CONCLUSION These results suggested that Andrographolide might improve lipid metabolism through downregulating the mRNA levels of SREBPs target genes.