The high fatality rate of sepsis has become a major threat to human health, and its pathogenesis has not been fully defined. Now we know immunologic dissonance is one of the main pathogenesis of sepsis. HMGB1 is a key factor for the immune imbalance. There are many kinds of receptors, such as RAGE, TLRs and CD24, which can mediate various signal transduction pathways by binding to the receptors, thus giving play to the immunomodulation function. The treatment of sepsis by traditional Chinese medicine single and compound has made some progress, and it remains to be further combined with modern medicine to cope with the challenges of sepsis.