Background: It has been reported that intestinal ischemia-reperfusion injury (IIRI) is closely related to inflammatory response, apoptosis and oxidative stress. Ellagic acid (EA) has been proved to have antioxidant and anti-inflammatory effects and can inhibit tumor angiogenesis. The purpose of this study was to investigate the protective effects of EA on IIRI in mice. Methods: A mouse model of IIRI was established by clamping the mesenteric artery. Effects and mechanisms of EA on IIRI were investigate by transcriptomics combined with functional experiments. Results: The symptoms of IIRI were reflected in significant increases in inflammatory factors such as TNF-α and IL-1β; significant increases in oxidative stress indicators such as MDA and GSH and decreases in SOD and promotion of the apoptotic protein Bax/Bcl-2. These indicators were significantly alleviated by EA. And after EA treatment, transcriptomics results identified AKT1 differentially expressed mRNAs mainly enriched in PI3K/AKT signalling pathway. Conclusion: This study illustrates the protective effects against IIRI, the possible mechanisms were also studied. This study provides new scientific information for the application of EA in IIRI therapy.