Objective: To investigate the patterns of syndrome changes and their possible material basis in mice 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 (Group X) and Sini Powder (Group S) were administered concurrently with the modeling process. General conditions, behavioral, and biochemical indicators were compared between the modeling mice (Groups M4 and M6) and the mice treated for 2 weeks (Groups S4 and X4) and 4 weeks (Groups S6 and X6) after chronic psychological stress. Results: Compared to Group M4 mice, the body weight, total distance and central distance in the open field test, serum NE concentration, and gastric Ghrelin expression were increased in Group S4 and X4 mice; the sugar water preference rate and serum D-xylose concentration were increased in Group S4 mice; compared to Group X4, the total distance in the open field test and serum D-xylose concentration were increased in Group S4 mice. Compared to Group M6 mice, the body weight, serum NE concentration, serum D-xylose concentration, and gastric Ghrelin expression were increased in Group S6 and X6 mice; the sugar water preference rate, total distance in the open field test, and active avoidance counts in the shuttle box test were increased in Group X6 mice, while the serum CORT concentration was decreased; compared to Group S6, the body weight, total distance in the open field test, serum D-xylose concentration, and gastric Ghrelin expression were increased in Group X6 mice. Conclusion: During the modeling process of chronic psychological stress in mice, the traditional Chinese medicine syndrome evolved from liver qi stagnation to liver qi stagnation with spleen deficiency, and the biological basis of syndrome changes may be the combined changes in serum CORT and NE concentrations and the decrease in gastric Ghrelin levels.