Objective To explore the mechanism of spleen deficiency in the pathogenesis of psoriasis-related inflammation.Methods The model mice with spleen deficiency was established by use of bitter cold and purging medicines combined with nutritional restriction, and then the model of psoriasis-like lesions induced by imiquimod.The mice were randomly divided into control group（Ctrl）,spleen deficiency group（PD）,imiquimod induced psoriasis-like model group（IMQ）and spleen deficiency combined with psoriasis model group（PD-IMQ）.The expression levels of psoriasis-related genes in skin lesions and small intestine were detected by real-time PCR,the contents of psoriasis-related cytokines and chemokines in peripheral blood were detected by liquid phase protein chip, and the diversity of gut microbiota was analyzed by 16 S sequencing.Results Inflammatory infiltration manifestations, like erythema and scales in PD-IMQ group were more serious, IL-17 a, IL-23,IL-6,TGF-β,IL-10 and IL-18 mRNA in skin lesions were significantly higher than those in IMQ group, and the contents of IL-17 A,MIP-1α,MIP-1β,MIP-2,MCP-1,MCP-3,RANTES,IP-10 and Eotaxin in peripheral blood of PD-IMQ group were significantly higher than those of IMQ group, while the content of ST2 was significantly lower.The levels of IL-17 a and ROR γt mRNA in small intestine of PD-IMQ group were significantly higher than those of IMQ group, while the richness and evenness of gut microbiota in PD-IMQ group were significantly lower than those in IMQ group.Compared with IMQ group, the relative abundance of AF12 bacteria was significantly increased, and the relative abundance of TM7,TM7-3,CW040 and F16 was significantly decreased.Conclusion Spleen deficiency may aggravate the response of imiquimod-induced psoriasis-like model to pro-inflammatory factors, which leads to severe lesions by up-regulating the expression of IL-17-related cytokines and chemokines and the abundance of lipid metabolism disorder-related bacteria AF12.