Introduction: Release of the danger signal, high mobility group box 1 (HMGB1), mediates the inflammatory response following hepatic ischemia-reperfusion (I/R) injury. Post-translational acetylation of HMGB1 is required for the active secretion of HMGB1. Since oxidative stress induces calcium signaling, we sought to determine if the calcium/calmodulin-dependent protein kinase (CaMK) IV pathway modulated HMGB1 acetylation and subsequent release during liver I/R. Methods: Cultured mouse hepatocytes from CaMKIV WT and KO mice were exposed to hypoxia (1% O2).