question: To explore the metabolic effect of chemerin, adipose-specific chemerin knockout (adipo-chemerin (-/-)) male mice were established and fed with 5-week normal diet (ND) or high fat diet (HFD), then the glycolipid metabolism index were measured and epididymal adipose tissue metabolomics were detected using untargeted liquid-chromatography-tandem mass spectrometry (LC-MS). Under HFD, adipo-chemerin (-/-) mice showed improved glycolipid metabolism (decreases of TC, LDL, insulin and HOMA-IR) compared with flox (control) mice. Furthermore, OPLS-DA score plots found metabolites separations between adipo-chemerin (-/-) mice and flox mice fed with ND and HFD. Under HFD, 28 metabolites were significantly enhanced in adipo-chemerin (-/-) mice, and pathway enrichment analysis suggested strong relationship of the differential metabolites with arginine and proline metabolism, phenylalanine metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis, which were directly or indirectly related to lipid metabolism, inflammation and oxidative stress. Under ND, taurine was increased in adipo-chemerin (-/-) mice, involving in taurine and hypotaurine metabolism and primary bile acid biosynthesis. In conclusion, the improved effect of chemerin knockdown on the glycolipid metabolism of HFD-feeding male mice might be associated with the increases of differential metabolites and metabolic pathways involving in lipid metabolism, inflammation and oxidative stress, which provided insights into the mechanism of chemerin from metabolomics aspect.