To investigate the antidepressant effect and possible mechanism of essential oil from Schizonepeta tenuifolia Briq.(EOST) on lipopolysaccharide (LPS)-induced depressive behaviors and NOD-like receptor pyrin domain-containing 3 (NLRP3) signaling pathway.In this study,the mice model with depression was established by intraperitoneal injection of LPS,and drug treated mice were intragastrically administered with EOST or fluoxetine.Sucrose preference test and splash test (ST) were performed at the end of the experiment.Interleukin 18 (IL-18) and tumor necrosis factor α(TNF-α) in serum were measured by enzyme-linked immunosorbent assay (ELISA),Nissl staining was used for observation of the changes of neurons in the hippocampus CA3 area of mice.The relative protein expression levels of NLRP3 inflammasome were detected by Western blot.The results showed that EOST 100,50 mg/kg significantly increased the preference of sugar water,prolong the grooming time of ST in mice,which demonstrated significant antidepressant-like behavioral effects.Additionally,it also reversed the upregulated IL-18 and TNF-α content in the serum of model mice,increased the mean IOD of Nissl bodies in the hippocampal CA3 region,down-regulated the expression levels of NLRP3,apoptosis-associated speck-like protein containing a CARD (ASC),cysteinyl aspartate specific proteinase-1 (Caspase-1),and ionized calcium binding adapter molecule 1 (Iba-1).EOST could combat the depression-like behaviors in depression model mice induced by LPS,which might be related to inhibit the activation of NLRP3 inflammasome and microglia,so as to alleviate neuroinflammation and neuronal damage.