Abstract: Objective To investigate behavioral, blood, and skin histopathological indexes in psoriasis mice. Methods BALB/ c mice were randomly divided into a control group, imiquimod-induced psoriasis model group (IMQ), and emotional stress complex imiquimod-induced psoriasis model group (ES+IMQ) and observed in an open field test (OFT) and Y maze test, and tested for serum substance P (SP) and skin histopathological indexes. Results In the OFT, Compared with the control group, both the IMQ group and ES+IMQ group covered shorter total distances, with decreased average velocity and extended residence time in the total areas and they had a shorter residence time and distance in the central area and extended distance and residence time in the edge area. In the Y maze test, the percentage of entries and percentage of residence time in the new arm decreased in both IMQ and ES+IMQ groups compared with control group. The serum SP concentration was increased in the IMQ group and decreased in the ES+IMQ group compared with the control group, and there was a statistical difference between the two model groups. Psoriasis-like skin histopathological changes were observed in both IMQ and ES+IMQ groups. The Baker score of changes were statistically different, but there were no statistical differences between the IMQ and ES+IMQ groups. Conclusions Under the experimental conditions, both IMQ and ES+IMQ group s showed decreased spontaneous activity, anxiety-like behavior, and impaired cognitive ability, which had an effect on serum SP levels, and they showed psoriasis-like skin histopathological changes. The ES+IMQ group showed more anxiety than the IMQ group, which was inversely proportional to the difference in serum SP levels, and the other indicators showed no significant differences.