Objective The absorption of substances into blood is mainly based on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported by the portal venous pathway can be biotransformed by liver. The substances in the mesenteric lymph fluid enter the blood circulation directly without biotransformation and affect the body. Therefore, exploring the changes of substances transported by the mesenteric lymphatic pathway and their harmfulness after drinking alcohol is particularly important. Methods In the experiment, male Wistar rats were divided into high, medium, and low- dosage alcohol groups (56, 28, and 5.6 degree liquor, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 days, 10 mL/kg/day. Then mesenteric lymph fluid was collected for liquid Chromatography-Mass Spectrometry (LC-MS) non-targeted metabolomic analysis and bioinformatics analysis. Results The metabolites in the mesenteric lymph fluid of the high-dosage alcohol group changed the most. Based on the enriched KEGG pathways of differential metabolites in mesenteric lymph, the pathways of differential metabolites between the high- dosage alcohol group and the control group were mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, synthesis of unsaturated fatty acids, etc.; And the differential metabolites are mainly associated with diseases: schizophrenia, alzheimer"s disease, lung cancer, and gastric cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, biosynthesis of valine, leucine and isoleucine, linoleic acid metabolism, cholesterol metabolism and other pathways; The differential metabolites are mainly related to diseases: schizophrenia disease, alzheimer"s disease, lung cancer, parkinson"s disease, etc. Conclusions After alcohol intake, a lot of metabolites transported by the intestinal lymphatic pathway significantly changed, especially in the high-dosage group. Furthermore, alcohol intake may cause inflammatory reactions and the occurrence of neurological diseases, psychiatric diseases and cancer diseases.