BackgroundPrevious studies found that metformin provided some renoprotection for diabetic renal damage. In the present study, we evaluated the effects of different doses of metformin on the expression of renal tissue nephrin in type 2 diabetes mellitus (T2DM) model rats and the possible mechanism underlying its protective effect in kidney podocytes. MethodsA high-fat diet combined with a low dose of streptozotocin was used to induce T2DM model rats. Diabetic rats were treated with 150, 300, or 500mg/kg metformin for 8weeks. At the end of the study, urine and blood samples were collected for measurement of different indices. Light microscopy and transmission electron microscopy were used to identify morphological changes. Renal expression of nephrin protein was assayed by immunohistochemical staining, whereas real-time polymerase chain reaction was used to detect renal nephrin (Nphs1) mRNA expression. ResultsMetformin treatment of T2DM rats produced dose-dependent significant reductions in urinary albumin and nephrin concentrations, glomerular basement membrane thickness (GBMT), and the foot process fusion rate (FPFR) compared with control T2DM model rats, whereas renal expression of nephrin protein and Nphs1 mRNA was dose-dependently increased by metformin treatment. ConclusionMetformin protects kidney podocytes in T2DM model rats by dose-dependently adjusting renal nephrin expression.