Objective: It was reported that High Mobility Group Box 1 (HMGB1), also known as the nuclear transcription factor, is a late mediator of inflammation. It was thought that HMGB1 has a prominent role in the activation of Tumor Necrosis Factor-a (TNF-alpha), Interleukin (IL)-1 beta and IL-8 which are proinflammatory mediators during inflammation. HMGB1 plays a role in progress, diagnosis and prognosis of immune system illnesses. Besides suppressing the immune system, Major Depressive Disorder (MDD) was indicated to cause changes in inflammatory processes. Biological determinants affecting the diagnosis, therapy, and prognosis of depression are quite limited. Therefore, new etiological models are needed to explain the pathophysiology of depression. There is no study in the literature investigating level of HMGB1 in MDD of the humans. This study aims to examine the role of inflammation in the etiology of depression based on the HMGB1 in patients with MDD.