Objective∶ To study the protective effect of Chaihuang Yishen granules on dysregulated lipids metabolism in kidney of rats with diabetic nephropathy（DN）.Method: Wistar rats were undergone uninephrectomy and a single intraperitoneal injection of streptozocin（STZ） to induce diabetes

and administratered with 0.56 g·kg-1 Chaihuang Yishen granules.At the end of 20 weeks

renal cortex of rats was removed and UPLC-QTOF MS was used to lipidomic study and to investigate the alterations of abnormal lipidome after administration of Chaihuang Yishen granules.Result: At the end of 20 weeks

multiple species of significantly decreased glycerophosphocholines

glycerophosphoethanolamines

glycerophosphoglycerols

glycerophosphoinositols and sphingomyelins

and clearly elevated cholesterol esters and triglycerides were identified in renal cortex of rats with DN.Among them

several lipid metabolites

such as 2 glycerophosphocholines and 4 sphingomyelins-SM（d18∶ 1/16∶ 1）

SM（C33∶ 1）

SM（C42∶ 2）

SM（C42∶ 3）

PC（36∶ 4） and PC（42∶ 10）

can be normalized towards their baseline by the intervention of Chaihuang Yishen granules with individually relative fold change: 1.38

1.50

1.29

1.23

1.15 and 1.30.Conlusion: Chaihuang Yishen gruanules can retard the development of DN in rats

which might be associated with its regulation in abnormally expressed lipids

especially sphingomyelins.