Abstract: Background and Objective: Berberine (BBR), an isoquinoline alkaloid has been used in treating many diseases. However, its effects on diabetic nephropathy inflammation have not been investigated. The purpose of this study was designed to evaluate the anti-inflammation effect of BBR on diabetic nephropathy. Methodology: The diabetic rat model was generated by a single intraperitoneal injection of streptozotocin (STZ). Diabetic rats were randomly assigned into the following five groups: Control, Diabetic Nephropathy (DN), losartan (30 mg kg–1, daily), BBR (100, 200 mg kg–1, daily). The BBR and losartan were given intragastricly for 8 weeks. At the end of the experiment, the urine of all rats in each group was collected in a 24 h period. The weight of each rat was recorded. Plasma and kidneys were collected. Kidneys was examined by Hematoxylin Eosin (HE) staining. Renal function parameters such as blood urea nitrogen, plasma creatinine and albuminuria excretion examination were also determined. The levels of blood glucose, malondialdehyde (MDA), triglycerides (TG) and total cholesterol (TCH) in serum were determined using commercial kits according to the manufacturer’s instructions. Lastly, real-time PCR and immunofluorescence were performed for measuring TNF-α and IL-6 expression in renal. Results: The BBR could improve renal function in diabetic rats (evidenced by mitigation of diabetes-induced changes in kidney index, albuminuria, urea nitrogen and creatinine clearance). The HE examination revealed that BBR-treated groups could ameliorate histological changes of diabetic nephropathy. Furthermore, macrophage infiltration was inhibited and inflammatory molecules were down-regulated by BBR. Conclusion: The BBR has renoprotective effects through anti-inflammatory action in diabetic nephropathy. The results indicated that BBR may function as an effective therapeutic agent for diabetic nephropathy and attenuate the progression of renal injury.