Objective To construct an animal model of post-stroke depression (PSD) based on the theory of “depression, stasis, phlegm”, with the aim of developing and validating an Objective assessment system. Methods Rats were divided randomly into five groups: control, depression, stroke, PSD, and Baishile decoction groups. A PSD syndrome-based animal model was established in rats using a combination of middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS). “Depression, stasis, phlegm” were then evaluated in the model rats using the Morris water maze, open field, forced swimming, and sucrose preference tests, and by detection of neurotransmitter levels, brain tissue pathology, tongue and forepaw color RGB values, and blood rheology. Results PSD rats exhibited significantly shorter target quadrant dwelling times, platform crossings, and climbing and rearing frequencies, a significantly lower sucrose preference, and a significantly higher immobility time in the forced swim test compared with control rats. Hematoxylin and eosin and Nissl staining revealed brain tissue damage in PSD rats. Serum and cerebrospinal fluid levels of 5-hydroxytryptamine ( 5-HT) were significantly decreased, glutamate levels were significantly increased, and tongue and forepaw RGB values were all decreased. Blood rheology showed a hypercoagulable state and blood lipid metabolism-related indicators were significantly abnormal. Rats in the Baishile decoction group showed significant improvements compared with the PSD group, including increased target quadrant dwelling times, number of platform crossings, and climbing and rearing frequencies, increased sucrose preference,decreased immobility time in the forced swim test, improved brain tissue pathology, increased serum and cerebrospinal fluid levels of 5-HT, decreased glutamate levels, increased tongue and claw RGB values, and varying degrees of improvement in blood rheology and blood lipid metabolism-related indicators. Conclusions The combination of MCAO and CUMS successfully established a syndrome-based animal model of PSD exhibiting the characteristics of “depression, stasis, phlegm”, with corresponding Objective assessment criteria.