Chronic stress caused by aversive and psychological stimuli induces emotional and cognitive abnormalities, precipitating the onset and relapse of human depression. Inflammation in the brain and periphery is thought to play a role in the pathophysiology of depression. We have demonstrated that chronic social stress causes neutrophil mobilization and its maintenance in mice. However, whether neutrophil mobilization is involved in behavioral alterations induced by chronic social stress remains unknown. Here we examine the role of neutrophil mobilization in chronic social stress-induced behavioral alterations by inhibiting or deleting C-X-C Motif Chemokine Receptor 2 (CXCR2), a chemokine receptor involved in neutrophil mobilization. Administration of CXCR2 antagonist once daily during and after chronic social stress prevented behavioral alterations induced by chronic social stress concomitantly with inhibiting neutrophil mobilization. Neutrophil-selective CXCR2 deletion in mice also abolished behavioral alterations in multiple behavioral tests after chronic social stress. These findings demonstrate that neutrophil mobilization is crucial for behavioral alterations induced by chronic social stress.