The anti-inflammatory effect of ellagic acid (EA) and its possible underlying mechanism in dextran sulfate sodium (DSS)-induced mouse chronic colonic inflammation were studied. It was observed that EA administration significantly alleviated the colonic inflammation phenotypes, including decreasing the disease activity index (DAI), enhancing the body weight loss, and improving the shortened length of the colon and pathological damage of colon tissue. Additionally, EA reshaped the constitution of the gut microbiota by elevating the ratio of Bacteroidetes along with Bacteroides and Muribaculaceae, while decreasing the proportion of Firmicutes. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUSt2) revealed that the metabolic function of the gut microbiota was also changed. Furthermore, mouse colon transcriptome analysis showed that the tight junction and peroxisome proliferator-activated receptor (PPAR) signaling pathways were activated and the expressions of related genes were upregulated after EA intervention. These results showed that EA could remodel the gut bacterial composition, change the intestinal epithelial cell gene expressions in mice, and consequently improve the colonic inflammatory symptoms.