Abstract: Objective 　To observe the changes of general status, lung histopathology, intestinal histopathology, colonic transcriptome and intestinal contents metabolome in mice infected with influenza A virus H1N1, and to study the mechanism of intestinal injury caused by H1N1 infection in mice. Methods 　C57BL/6J mice were infected with influenza virus PR8, lung tissue, colon tissue and cecum contents were retained on day 7 after infection, lung index was calculated, colon length was measured, lung and intestinal histopathology was observed by hematoxylin-eosin staining, colonic transcriptome sequencing was performed by RNA-seq, and cecum contents were detected by non-targeted metabolomics. Results 　Mice in Model group showed reduced body weight and activity, increased lung index, shortened colon length, and histopathological damage to the lung and colon compared with mice in Control group. There were 1609 differentially expressed genes and 437 differential metabolites between mice in Control group and Model group,the pathways they were jointly enriched to include arachidonic acid metabolic pathway and tryptophan metabolic pathway. Conclusion 　Influenza A virus infection may cause intestinal injury in mice by altering gene expression levels in the colon and metabolites in the cecum.