Abstract: OBJECTIVE To investigate therapeutic effects of plumbagin(PLB) on nonalcoholic fatty liver disease (NAFLD). METHODS Adult C57BL/6J mice were divided into four groups: control group (standard diet, 15% fat), high fat diet group(HFD, 58% fat), HFD+PLB(5 mg·kg^-1·d^-1)group, HFD+PLB(15 mg·kg^-1·d^-1) group. The HFD model was established for six weeks, and PLB was administered four weeks. Then the mice were killed to study the lipid accumulation in the liver by HE staining and oil red staining. The effects of liver lipid metabolism and gluconeogenesis related gene expression were studied by qRT-PCR. Finally, the expression of activator protein(AP-1) related subunits were studied by Western blotting. RESULTS PLB could significantly reduce body weight and blood glucose level of mice. HE staining and oil red staining showed that PLB could significantly reduce the liver lipid accumulation of mice. PLB significantly reduced the expression of lipid metabolism and gluconeogenesis related genes, and inhibited the expression of AP-1 subunits c-Jun, c-Fos and Fra1. CONCLUSION PLB can significantly inhibit fat accumulation, maintain fat metabolism and glucose homeostasis, and inhibit the inflammatory response of AP-1 in liver cells of HFD mice.