Aim To investigate the nephroprotective activity of berberine in diabetic nephropathy (DN) mice.Methods Diabetic nephropathy was induced by intraperitoneal injection with 55 mg · kg1 streptozotocin (STZ),Berberine was administered at daily doses of 50, 100 and 200 mg · kg1 by gavage for 8 weeks.To detect serum creatinine and blood urea nitrogen (BUN) levels, blood were collected after the last dose of berberine, renal cortex was separated on ice after heart perfusion by precooled normal saline.The specimen was stored in80℃ for the next experiments, and some of the kidney tissue were immobilized by 4% paraformaldehyde solution and 3% glutaraldehyde solution for the preparation of paraffin tissue slides and electron microscope biopsy respectively.After that, PAS staining and electron microscope were used to observe the glomerular morphology changes; ELISA was used to measure proinflammatory chemokines and cytokines levels in renal cortex.Real time RTPCR was taken to detect the level of nucleotide binding oligomerzation domain 2 (NOD2) mRNA, Western blot was used to test the expression of NOD2 and autophagy marker light chain 3 (LC3) in renal cortex.Results Histopathological changes and the increase in serum creatinine and BUN in DN mice were significantly ameliorated by berberine in a dosedependent manner.Additionally, The expression of tumor necrosis factorα (TNFα), interleukin6 (IL6) and intercellular adhesion molecule1 (ICAM1) was markedly suppressed by berberine, indicating the inhibition of inflammatory response.Treatment of DN mice with berberine also significantly reduced the expression of NOD2 and LC3 in the kidneys.Conclusion The current study showed the nephroprotective activity of berberine in DN mice could be attributed to the inhibition of inflammation and autophagy