Conclusively, all of these results give more support to the hypothesis that the CRS-induced neuroinflammation mediated by hippocampal Iba-1 and HMGB1 was involved in the pathogenesis of depression, and the antidepressant effect of acupuncture might be through modulating the neuroinflammation mediated by hippocampal Iba-1 and HMGB1. Here, HMGB1 is linked to major depressive disorder.