Abstract: 【Objective】Based on metabolomics，the effects of lysine（Lys）levels on the differential metabolites of Guizhou yellow chicken’s feeding center was explored，which could provide theoretical basis for exploring the optimal amount of Lys added to the diet of Guizhou yellow chicken.【Method】A total of 400 healthy 1-day-old Guizhou yellow chickens were selected and randomly divided into 4 groups. Four corn-soybean meal diets with different Lys levels （0.7%，0.9%，1.1% and 1.3%）were set up and fed to the 4 groups of Guizhou yellow chickens respectively. The body weight and feed intake were recorded. The experiment ended at 6 weeks of age. Hypothalamic tissues of Guizhou yellow chickens in the 0.7%，0.9%，and 1.3% groups were collected for liquid chromatography-mass spectrometry（LC-MS） analysis.【Result】The average daily feed intake（ADFI）of Guizhou yellow chickens aged 0-6 weeks was the highest in the 0.9% group and the lowest in the 1.3% group，and the 0.7%，0.9% and 1.1% groups were significantly higher than the 1.3% group（P<0.01，the same below）. The average daily weight gain（ADG）of Guizhou yellow chickens aged 0-6 weeks was the highest in the 0.9% group and the lowest in the 1.3% group，and the 0.9% and 1.1% groups were significantly higher than the 0.7% and 1.3% groups. A total of 18，25 and 29 differential metabolites were screened out in the 0.7% vs 0.9% group，the 0.9% vs 1.3% group and the 0.7% vs 1.3% group respectively. In the 0.7% vs 0.9% group and the 0.9% vs 1.3% group，N-（2-furoyl）glycine and D-mannose were significantly different（P<0.05，the same below）. Dmannose was up-regulated in the 0.7% vs 0.9% group and down-regulated in the 0.9% vs 1.3% group. KEGG signaling pathway enrichment results showed that in the 0.7% vs 0.9% group，the significantly enriched signaling pathways were glutathione metabolism，taurine and hypotaurine metabolism，D-glutamine and D-glutamate metabolism，and β-alanine metabolism. In the 0.9% vs 1.3% group，the significantly enriched signaling pathways were ABC transporters and aminoacyl-tRNA biosynthesis. In the 0.7% vs 1.3% group，the significantly enriched signaling pathways were ferroptosis， glutathione metabolism，thyroid hormone synthesis，neomycin，kanamycin and gentamicin biosynthesis.【Conclusion】 Appropriate Lys levels activate signaling pathways such as glutathione metabolism and ABC transporters. Lys may affect the feeding behavior of Guizhou yellow chickens by regulating immunity，anti-inflammation and redox balance. The dynamic changes of metabolites such as D-mannose show a close connection between nutritional signals and neural regulation. Lys may participate in protein synthesis or play a regulatory role in central nervous metabolism.