Background　Interleukin 1 receptor-associated kinase M(IRAK-M) is an important negative regulator of Toll-like receptor(TLR) signaling pathway which can limit excessive inflammatory response by inhibiting NF-κB signaling pathway.　Objective　Studies regarding mechanisms underlying the regulation of inflammatory response by IRAK-M would provide new insights to understand sepsis-induced immune-paralysis.　Content　Sepsis, one of systemic inflammatory and immune reactions to multiple pathogens, is a major cause of death in intensive care units worldwide. Chronic sepsis is followed by immune paralysis, a state that immune system losses reaction to pathogens. IRAK-M is detected in monocytes, phagocytes, and epithelium, and negatively modulates TLR activation mainly through transforming growth factor-β activated kinase-1(TAK1)-depedent pathway. Overactivation of TAK-1 and downregulation of IRAK-M are two critical events in early inflammatory reactions in sepsis. IRAK-M also binds to MyD880-IRAK-4 complex, an important component in mitogen-activated protein kinase/extracellular signal-regulated kinase-kinase 3(MEKK3)-dependent pathway, to participate in activation of NF-κB, and subsequent immune paralysis in sepsis. It has been demonstrated that IRAK-M is regulated by various factors, including cytokines, nicotinic acetylcholine receptors, glucocorticoids, etc, and in sepsis, IRAK-M is upregulated, and plays vital roles in pathophysiology of sepsis.　Trend　IRAK-M may play an important role in immune status and immunoregulation in sepsis, suggesting that IRAK-M may be a potential therapeutic target for sepsis.