Objective To investigate the patterns of syndrome changes and their possible material basis in mouse models of chronic psychological stress during the modeling process. Methods A chronic unpredictable mild stress (CUMS) method was employed to prepare a model of chronic psychological stress in mice. After 2 weeks of modeling, Xiaoyao powder (XYS group) and Sini powder ( SNS group) were administered concurrently with the modeling process. General conditions, behavioral, and biochemical indicators were compared between the modeling mice (M4 and M6 group) and the mice treated for 2 weeks (S4 and X4 group) and 4 weeks (S6 and X6 group) after chronic psychological stress. Results Compared with M4 group mice, body mass, total distance and central distance in the open field test, serum NE concentration, and gastric Ghrelin expression were increased in S4 group and X4 group mice, and sugar water preference rate and serum D-xylose concentration were increased in S4 group mice. Compared with X4 group mice, total distance in the open field test and serum D-xylose concentration were increased in the S4 group mice. Compared with M6 group mice, body mass, serum NE concentration, serum D-xylose concentration, and gastric Ghrelin expression were increased in group S6 and X6 group mice; sugar water preference rate, total distance in the open field test, and active avoidance counts in the shuttle box test were increased in X6 group mice, while their serum CORT concentration was decreased. Compared with S6 group mice, body mass, total distance in the open field test, serum D-xylose concentration, and gastric Ghrelin expression in X6 group mice were increased. Conclusions During the process of modeling chronic psychological stress in mice, the traditional Chinese medicine syndrome evolved from liver qi stagnation to liver qi stagnation with spleen deficiency. The biological bases of the syndrome changes may be the combined changes in serum CORT and NE concentrations and the decrease in gastric Ghrelin levels.