The study investigated the effects of Ganoderma lucidum polysaccharide (GLP) on diabetic nephropathy (DN) in mice.After successfully establishing a DN mouse model,GLP intervention was administered.The fasting blood glucose and 24-hour urinary protein content of the mice were measured,and the levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were determined.Eosin and Masson′s trichrome staining were used to observe the renal pathological morphology.Enzyme-linked immunosorbent assay was employed to measure the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10).Western blot was utilized to detect the expression of receptor for advanced glycation end-products(RAGE),collagen type IV(COL-IV),and inducible nitric oxide synthase(iNOS).Mice in the DN group exhibited increased levels of fasting blood glucose,24-hour urinary protein,BUN,and Scr as well as elevated levels of TNF-α and IL-6 in renal tissue (P< 0.05),and decreased levels of serum IL-10 (P< 0.05).The expression of RAGE,COL-IV,and iNOS proteins was also increased (P< 0.05).In contrast,mice in the treatment group showed improvements in pathological damage and fibrosis,with quantitative indicators showing significant amelioration.GLP could ameliorate DN in mice,and the mechanism is associated with the inhibition of the RAGE signaling pathway.