To reveal the mechanism of artemisinin in treating the metabolic disorders induced by a high-fructose diet in mice based on the changes of serum metabolites.Methods:The levels of glucose，triglycerides，and cholesterol in the serum were measured for the mice in the control，high-fructose diet，artemisinin，and positive drug groups.Metabolic profiling was carried out by ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS)，and the differential metabolites were screened out by univariate statistical analysis.Furthermore，Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment was conducted for the differential metabolites.Results:Artemisinin significantly reduced the high-fructose diet-induced rise in the serum level of triglycerides in mice.The metabolic profiles were different among groups.Forty-two and 45 differential metabolites were screened out in the positive and negative ion modes，respectively.Changes occurred in the pathways such as linoleic acid metabolism，retrograde endocannabinoid signaling，and biosynthesis of unsaturated fatty acids.Conclusion:Artemisinin can restore the metabolic disorders caused by a high fructose diet，which mainly involves the lipid metabolism.