Objective To construct an animal model of type 2 diabetes nephropathy (DN) with the combination of disease and syndrome of "dampness syndrome" in traditional Chinese medicine, and to conduct macroscopic characterization and microscopic index evaluation of the model. Methods Based on the spontaneous db/db mouse disease model, 60% high-fat diet was used to construct the internal dampness syndrome and explore the construction of an animal model of diabetes nephropathy combined with damp syndrome. Observe the general condition and body weight of each group of mice; Measure biochemical indicators such as urinary microalbumin creatinine ratio, blood glucose levels, renal function, and glucose and lipid metabolism in mice; HE, PAS, Masson, Oil Red O staining were used to observe the pathological changes in the kidneys; PCR technology is used to detect the levels of microinflammation and fibrosis in renal tissue; Immunofluorescence assay was used to detect the polarization degree of macrophages in renal tissue; HE staining and PCR technology were used to detect the mucosal barrier of intestinal tissue; Collect mouse feces and use LC-MS technology to detect fecal metabolome. Results Compared with the normal group and the diabetic kidney group, the diabetic kidney dampness syndrome group showed obvious phenomena such as smooth fur and oily skin, loose stools, mental fatigue, fatigue, clumping and curling, polyuria, and a significant increase in body weight (P<0.05), indicating the successful construction of the dampness syndrome model; In terms of biochemical indicators, the TC index in the group with diabetic kidney dampness syndrome was significantly increased (P<0.05); In terms of pathological changes in renal tissue, HE staining in the group with diabetic kidney dampness syndrome showed significant homogeneous thickening of the glomerular basement membrane, significant proliferation of the mesangial matrix, PAS staining showed significantly aggravated glycogen deposition (P<0.05), and Oil red staining showed significant lipid droplet deposition; At the level of fibrosis, Masson staining in the diabetic kidney dampness syndrome group showed significant collagen blue staining, increased interstitial fibrosis in the glomeruli (P<0.001), and significantly increased expression levels of pro-fibrotic factors α-SMA, CTGF, FN, and TGF-β mRNA (P<0.001); At the micro inflammatory level, the inflammatory factors TNF-α, MCP-1, and IL-6 in the group with diabetic kidney dampness syndrome were significantly increased (P<0.001), and the polarization of M1 macrophages was significantly enhanced (P<0.05); At the level of intestinal microbiota, HE staining of intestinal tissue showed aggravated intestinal damage in the group with diabetic kidney dampness syndrome. The expression levels of Zo-1 and Occludin mRNA in the intestine of the group with diabetic kidney dampness syndrome were significantly reduced (P<0.001). Fecal metabolomics results showed that dampness syndrome modeling affected related pathways, including betaine biosynthesis, caprolactam degradation, phenylpropanoid biosynthesis, styrene degradation, alpha linolenic acid metabolism, phenylalanine metabolism, sphingolipid metabolism, tryptophan metabolism, and biosynthesis of tropane, piperidine, and pyridine alkaloids. Conclusions The method of feeding the compound spontaneous db/db mouse disease model with 60% high-fat diet can successfully construct the type 2 diabetes nephropathy "dampness syndrome" disease syndrome combined animal model. This study provides an ideal animal model for the follow-up in-depth exploration of the construction of the animal model of type 2 diabetes nephropathy with damp syndrome and the pharmacodynamics of Chinese herbal compound on DN.