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OBJECTIVE:To identify the antidepressant effect of Xingnao Jieyu (XNJY) decoction on a post-stroke depression (PSD) rat model and the underlying molecular mechanism.METHODS:We established a rat PSD model by middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stress (CUMS).Healthy SD rats were randomly divided into six groups:sham,PSD,fluoxetine (Flu),and XNJY groups at low,middle,and high doses.The sham group underwent sham operation,while the other groups underwent MCAO+CUMS.The Flu and XNJY decoction groups were intragastrically administered with Flu or different doses of XNJY for 21 consecutive days.Histopathological changes in the cortex and hippocampus were observed by staining with hematoxylin and eosin and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling.Iba1 positive cells were evaluated by immunofluorescence assay.The expressions of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),interleukin-1β (IL-1β),5-hydroxytryptamine (5-HT),and norepinephrine (NE) in the cortex and hippocampus were measured by enzyme linked immunosorbent assay.RESULTS:The PSD group rats had a significant decrease in body weight,consumption of sucrose water,and locomotor activity but an increase in immobility time during a forced swimming test (P ＜ 0.01) compared with sham group.Flu and different doses of XNJY significantly recovered these indices (P ＜ 0.01).XNJY also inhibited neuronal damage and apoptosis in the cortex induced by PSD (P ＜ 0.01).Furthermore,XNJY reduced the number of Iba1 positive cells and the expressions of TNF-α,IL-6,and IL-1β,in addition to recovered the levels of 5-HT and NE in the cortex and hippocampus (P ＜ 0.01).CONCLUSION:The alleviation of neuroinflammation might be an important mechanism of the XNJY decoction against PSD.Thus,XNJY might be a promising candidate for the treatment of PSD.