Objective: To construct and evaluate a mouse model of pressure overload-induced heart failure with dampness syndrome.Methods: A total of 21 C57BL/6 mice were randomly divided into three groups: sham operation group , heart failure group , and heart failure with dampness syndrome group . The sham group underwent thoracotomy without aortic constriction, while the TAC group underwent aortic arch constriction to induce pressure overload-induced heart failure. Both groups were housed in a normal environment. The TAC-D group, in addition to undergoing TAC surgery, was placed in a controlled temperature and humidity chamber for 8 hours daily to induce dampness syndrome, with the remaining time spent in a normal environment. This protocol was maintained for 8 weeks. The macroscopic manifestations of the mice were assessed using the "Evaluation Scale for Dampness Syndrome Animal Models in Traditional Chinese Medicine." Modern medical techniques were employed to measure cardiac function, myocardial histopathology, immune homeostasis, serum NT-proBNP, and lipid levels. Additionally, fecal 16S rDNA sequencing and serum non-targeted metabolomics were conducted to develop novel evaluation indicators for the heart failure with dampness syndrome mouse model.Results: The TAC-D group exhibited significant manifestations of fatigue, lethargy, reduced responsiveness to external stimuli, and anal soiling. Both heart failure groups demonstrated marked cardiac dysfunction, myocardial injury, immune homeostasis imbalance, elevated serum NT-proBNP levels, and reduced lipid levels, with these changes being more pronounced in the TAC-D group. Fecal 16S rDNA sequencing and serum non-targeted metabolomics revealed significant alterations in the gut microbiota and metabolites following dampness syndrome induction. Lefse analysis (LDA>2) identified five bacterial genera—Enterorhabdus, Eubacterium, Corynebacterium, Christensenellaceae, and Erysipelatoclostridium—that were significantly enriched in the TAC-D group. Metabolomics KEGG enrichment analysis indicated that differential metabolites in the TAC-D group were primarily enriched in glycerophospholipid metabolism, arachidonic acid metabolism, and bile secretion pathways. Pearson correlation analysis revealed significant negative correlations between the bacterial genera Eubacterium and Erysipelatoclostridium and metabolites involved in arachidonic acid metabolism, including 16R-HETE, 6-keto PGE1, PE-NMe2(16:1(9Z)/20:3(8Z,11Z,14Z)), Prostaglandin F2a, TXB2, Oxoglutaric acid, and 12(R)-HETE.Conclusion: The combination of aortic arch constriction and controlled temperature and humidity environment successfully established a mouse model of pressure overload-induced heart failure with dampness syndrome. The "Evaluation Scale for Dampness Syndrome Animal Models in Traditional Chinese Medicine," cardiac function, serum NT-proBNP, myocardial histopathology, and immune homeostasis can serve as conventional evaluation indicators for this model. Additionally, the incorporation of gut bacterial genera Eubacterium and Erysipelatoclostridium and arachidonic acid metabolism disturbances further develops an innovative evaluation system for the heart failure with dampness syndrome mouse model.