Background & Aim: As the leading cause of liver dysfunction all over the world, non-alcoholic fatty liver disease (NAFLD) is a clinical metabolic syndrome with fatty accumulation in hepatocytes,nevertheless, without alcohol consumption.In recent years, morbidity of NAFLD has grown in Eastern and Western countries, and the diet composition has become an important health issue.NAFL and NASH are involved in the spectrum of NAFLD, NASH is easier develop into liver fibrosis, cirrhosis, and even hepatocellular carcinoma.In clinical, liver biopsy as the gold standard to assess levels of steatosis,inflammation and fibrosis in NAFLD is invasive, costly and associated with possible complications.Several kinds of noninvasive biomarkers for evaluating NAFLD have been investigated but none performed well enough.Therefore, it is still interest to discover noninvasive method to help detecting NAFLD.Recently published data showed that quality of fatty acids (FA) accumulated in liver is associated with the degree of liver damage in NAFLD.Study about serum FA variation in NAFLD is limited.Our study aims to investigate the correlation between serum FA composition and the hepatic steatosis, inflammation, hepatocellular ballooning scores and even liver FA composition in the influence of high-fat diet (HFD) in mice.Methods: ICR mice (10mice/group) were fed with HFD or control diet (CD) for 4, 6 or 8weeks.Livers were collected for pathology and NAFLD activity score (NAS) analysis.Serum and liver FA composition was analyzed by gas chromatography (GC).The correlation analysis was determined with Pearson correlation coefficient.Results: Induced by HFD, mice got fatty liver disease of different level without obvious fibrosis, and the liver damage level increased as the HFD feeding time went by.NAFL could be diagnosed at the 4th week of HFD feeding and NASH could be diagnosed at the 6th and 8th week.Liver fibrosis has not occurred from the beginning to the end of the experiment.FA composition analysis in mice serum and liver showed that levels of C16∶0, C18∶0, C18∶1, C18∶2 and C20∶4 were much higher than the others.During the HFD feeding, all of the tested FA individuals in liver and serum showed the same variation tendency except for C14∶0, C15∶ 0, C17∶0 and C20∶ 4.The concentration of C12∶0, C18∶1, C18∶2, C18∶3, C20∶1, C20∶3 and n-6 FA together with the ratio of (C20∶5+C22∶6)/C18∶3 (represents for n-3 pathway) in mice serum altered more and more severe as HFD feeding time went on, whats more, they correlated to the hepatic corresponding FA, steatosis, inflammatory and hepatocellular ballooning scores significantly.Conclusions: Induced by HFD, FA variation in serum correlated to liver FA variation, steatosis, inflammation and hepatocellular ballooning levels in mice.A logical hypothesis comes up: Serum FA variation maybe a preliminary biomarker of fatty liver disease caused by high-fat intake.