Intestinal ischemia-reperfusion(IIR)injury is a clinical critical disease with high mortality during perioperative period,and the existing prevention and treatment methods are limited.Latest studies have shown that intestinal microbial metabolites are involved in the regulation of IIR injury through epigenetic modification.The existing evidence suggests that the targeted microbial-epigenetic interaction network may provide a new prevention and treatment strategy for IIR injury,but the related clinical transformation research still needs to be deepened.This article reviews the characteristics of intestinal flora imbalance and the change rule of metabolites after IIR,the molecular mechanism of microbial metabolites regulating inflammation and cellular apoptosis through TLR3/NF-κB signaling pathway,non-coding RNA,and the protective effect of his-tone modification on intestinal barrier function and distant organs.