High mobility group box-1 (HMGB1) was originally identified as an intranuclear chromatin DNA binding protein. HMGB1 has unique feature in its mobilization, translocation and release. Responding to ischemic/hypoxic and traumatic injuries, HMGB1 may be released from different types of cells through cytosolic compartment. In the previous studies, we demonstrated that HMGB1 was released from neurons by ischemic as well as hemorrhagic injuries in the brain, leading to the disruption of integrity of blood-brain barrier (BBB). Intravenous injection of anti-HMGB1 mAb protected BBB and ameliorated brain damage by reducing inflammatory responses including cytokine expression. In the epileptic animal model, we found that therapeutic anti-HMGB1 mAb administered systemically accumulated on vascular endothelial cells while protecting brain inflammation and neural damage. These findings strongly suggested that vascular endothelial cells may be one of major targets of anti-HMGB1 mAb action. In this symposium, I will show our recent data on HMGB1 mobilization in vascular endothelial cells induced by different stimuli, associated with cytokine production and cellular responses. The results imply that HMGB1 released from endothelial cells played fundamental roles in triggering inflammatory responses.