Objective：To study the therapeutic properties and possible mechanism of Ganoderma lucidum polysaccharides（GL-PS）on diabetic nephropathy in streptozotocin（STZ）-induced mice. Methods：STZ［100 mg/（kg·d）］ was administered by intraperitoneal injection to induce diabetic nephropathy model in mice. The mice were randomly divided into 6 groups（n=10 in each group）：the normal group，model group，GL-PS groups with GL-PS dose of 50，100 and 200 mg/kg，and the telmisartan（TMS）group（5 mg/kg）. After 8 continuous weeks of intragastric administration，the mice uric，blood and renal were collected，and some physiological and biochemical indexes were determined by kits. Renal pathology was examined by hematoxylin-eosin（HE）staining. Protein expressions of NOD-like receptor 3（NLRP3），nuclear factor（NF）-κB and interleukin（IL）-1β in renal tissues were also analyzed by Western blot. Results：Compared with the model group，GL-PS and TMS obviously decreased the levels of blood urea nitrogen（BUN），serum creatinine（SCr），serum uric acid（SUA），glucose（GLU），total cholesterol（TC），triglyceride（TG），and interleukin（IL）-1β，IL-18，IL-6，as well as tumor necrosis factor（TNF）-α and urinary protein contents excreted during 24 h；significantly increased the high-density lipoprotein cholesterol（HDLC）level in STZ-induced diabetic nephropathy mice. HE and Western blot results indicated that GL-PS and TMS also obviously alleviated renal inflammatory reaction，inhibited NLRP3/NF-κB inflammasome activation，and down-regulated the protein expression of IL-1β. Conclusion：GL-PS has remarkable therapeutic properties on diabetic nephropathy in mice. The possible mechanism may be related to suppressing of inflammasome activation and improving of renal function.