The Xingnao Jieyu capsule has been shown to effectively relieve neurologic impairments and lessen depression. It remains poorly understood whether this capsule can be used to treat post-stroke depression. Thus, in the present study, we established a rat model of post-stroke depression using left middle cerebral artery occlusions in combination of chronic unpredictable stress and solitary housing during development. Experimental rats received intragastric perfusion with 0.82, 0.41, and 0.20 g/kg Xingnao Jieyu capsules separately dissolved in 2 mL distilled water. Fluoxetine served as a positive control. The treatment was conducted over 28 days. Sugar water consumption test, open-field test, real-time fluorescent quantitative PCR and immunohistochemical staining results demonstrated that intragastric perfusion with various doses of Xingnao Jieyu capsules increased sugar water consumption, voluntary behaviors and synaptotagmin mRNA and protein expression in rats with post-stroke depression. These therapeutic effects were similar to those of fluoxetine. These results indicate that Xingnao Jieyu capsules upregulate synaptotagmin expression in hippocampi of rats with post-stroke depression, and exert antidepressant effects. It remains poorly understood whether this capsule can be used to treat post-stroke depression. It Xingyao Jieyu capsule has been shown to relieve neurologic impairments and lessen depression. It, in the present study, we established a rat model of post-stroke depression. using left middle cerebral artery occlusions in combination of chronic unpredictable stress and solitary housing during development. Experimental rats were intragastric perfusion with 0.82, 0.41, and 0.20 g / kg Xingnao Jieyu capsules dissolved in 2 mL distilled water. Fluoxetine served as a positive control The treatment was conducted over 28 days. Sugar water consumption test, open-field test, real-time fluorescent quantitative PCR and immunohistochemical staining results for that intragastric perfusion with various doses of Xingnao Jieyu capsules increased sugar water consumption, voluntary behaviors and synaptotagmin mRNA and protein expression in rats with post-stroke depressio These results indicate that similar to those of fluoxetine.