Objective To construct a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern and evaluate the model from multiple dimensions and directions, expects to provide research support for the study of traditional Chinese medicine (TCM) treatment of psoriasis with spleen deficiency and dampness obstruction pattern. Methods A mouse model of spleen deficiency and dampness obstruction pattern was established by feeding a high-fat diet, a mouse model of psoriasis vulgaris was established by externally applying imiquimod ointment, and a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern was constructed by combining the above two models. Indications of spleen deficiency and dampness obstruction pattern were evaluated by comparing the body mass, food intake and water intake of mice in each group. The severity of psoriasis in mice was evaluated by comparing the area of skin lesions, PASI score, the value of transdermal water loss (TEWL), and histopathological morphological changes of skin under HE staining in each group. Flow cytometry was used to detect the expression in various cell types to evaluate the degree of inflammatory response of psoriasis in mice. Observation of adiposity index, changes in the histopathological morphology of liver tissue under HE staining, changes in the mRNA expression levels of related factors in liver tissue and adipose tissue of epididymis of mice detected by RT-qPCR, and changes of ABCA1 protein expression level of skin detected by Western Blot were used to evaluate the lipid metabolism disorders in mice. Results Compared with the mice in the psoriasis vulgaris model group, the mice in the model of psoriasis with pattern of spleen deficiency and dampness obstruction had significantly higher body mass (P<0.001), significantly lower food intake (P<0.005), and the symptoms of pattern of spleen deficiency and dampness obstruction such as greasy fur, mental fatigue, etc. appeared. The TWEL were significantly increased (P<0.001), and the PASI scores also significantly increased (P<0.001). HE results were found psoriasis-like manifestations including hypertrophy of the spinous layer and clubbed hyperplasia. The expression of CD11bhighLy6G+ neutrophil subpopulation, CD11binLy6Chigh monocyte subpopulation, CD11binCD11chigh classical dendritic cell subpopulation, F4/80-CD11c+ dendritic cell subpopulation was significantly increased (P< 0.001). HE staining suggested that the cellular morphology of liver showed obvious vacuolated degeneration, and the index of subcutaneous white adiposity and epididymal adiposity index were both significantly increased (P< 0.005). The mRNA levels of FABP4 and CD36 in liver tissue were significantly elevated (P<0.005, P<0.001), while the mRNA expression levels of ABCA1 and PPARγ in epididymal fat tissue were decreased (P<0.05, P< 0.01). ABCA1 protein level in skin increased (P>0.05). Conclusion The mouse model of psoriasis with spleen deficiency and dampness obstruction pattern can be used as a reliable animal model for combining disease and pattern, which can provide a reference for further exploration of TCM in the treatment of psoriasis with spleen deficiency and dampness obstruction pattern. [ABSTRACT FROM AUTHOR]