To observe the effect of coptisine on the fatty liver disea-se of SD (Sprague Dawley) rats and investigate the mechanism. Methods:The SD fatty liver rats were induced by high fat diet. Rats were randomly divided into normal control group，high fat model group，coptisine low and high dose groups (10 mg/kg or 50 mg/kg). After 30 days of administration，the body weight，liver index，triglyceride (TG)，liver function (alanine transaminase (ALT)，aspartate aminotransferase (AST) and liver pathology of each group were analyzed. The expression of coptisine to adenosine monophosphate activated protein kinase (AMPK) protein in human HepG 2 cell line was estimated by Western Blot (WB)，the expression of carnitine palmitoyltransferase-1 messenger Ribose Nucleic Acid (CPT-1 mRNA) and hydroxy-methylglutaryl coenzyme A messenger Ribose Nucleic Acid (HMG-CoA mRNA) was analyzed by Real Time-Poly Polymerase Chain Reaction (RT-PCR)，and the content of adenosine monophosphate (AMP) in the cell was determined by high performance liquid chromatography (HPLC). Results:Compared with the high-fat diet group，the two groups of coptisine intervention reduced the TG level of blood lipid，AST，and triglyceride content in liver，and significantly improved the histological morphology of liver in high-fat feeding. The high-dose group was better than the low-dose group. The HepG2 cells were treated with coptisine，AMP concentration was significantly increased，the activation of AMPK protein phosphorylation was increased，the expression of CPT-1 mRNA expression was also increased，and the expression of HMG-CoA mRNA was inhibited (P<0.05). Conclusion:The coptisine can remarkably improve fatty liver in rats，and its mechanism may be related to the increasing of AMP concentration and the activation of AMPK signaling pathway.