High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein that under normal conditions binds and bends DNA and facilitates gene transcription. In response to infection or injury, HMGB1 is actively secreted by innate immune cells and/or released passively by necrotic or damaged cells to function as an alarmin (Andersson U et al. 2000; Scaffidi P et al. 2002; Bonaldi T et al. 2003; Chen G et al. 2004; Lamkanfi M et al. 2010; Beyer C et al. 2012; Yang H et al. 2013). Earlier studies reported that HMGB1 did not diffuse out of cells undergoing apoptosis as HMGB1 was found to be tightly associated with the chromatin in apoptotic cells, even when the cell membrane was permeabilized artificially with detergents (Scaffidi P et al. 2002). This finding is in agreement with the general observation that apoptosis does not promote inflammation. However, further work showed that cells that undergo apoptosis do release HMGB1 (Bell CW et al. 2006; Yamada Y et al. 2011; Spencer DM et al. 2014). In human apoptotic cells (acute myeloid leukemia H60, HeLa, Jurkat T lymphocyte, pancreatic carcinoma PANC1 cell lines) HMGB1 was found to translocate into membrane-bound vesicles which are generated and released by cells during apoptosis (Spencer DM et al. 2014; Schiller M et al 2013). Outside the cell, HMGB1 can serve as an alarmin to activate innate immune responses including chemotaxis and cytokine release in both normal and aberrant immunity (Andersson U et al. 2000; Zetterström CK et al. 2002; Voll RE et al. 2008; Harris HE et al. 2012; Diener KR et al. 2013; Yang H et al. 2013).