Considering pathogenic known role of the NLRP3 inflammasome in endotoxic shock (Mariathasan et al., 2006; Mariathasan et al., 2004), together with EP’s anti-inflammatory effect, here we postulate that ethyl pyruvate might inhibit HMGB1 release and thus play a protective role in sepsis- and endotoxemia-induced lethality by inhibiting the NLRP3 inflammasome activation. Here, HMGB1 is linked to Sepsis.