Abstract: Objective：To investigate the effects of berberine on the alleviation of the renal damage induced by high fat diet and its correlation with toll-like receptors. Methods：Fifty male Wistar rats were randomly divided into the five groups. The normal feeding group (NF group), the normal feeding and berberine treatment group (NF+BBR group), the high-fat feeding group (HF group), the high-fat feeding and low-dose berberine treatment group (HF+LBBR group), and high-fat feeding and high-dose berberine treatment group (HF+HBBR group). Except the two normal feeding group, the rats in other three groups were fed with high-fat diet for 8 weeks. After 4 week, the three berberine intervention groups received different concentrations of berberine, respectively. At the end of the experiment, the blood samples and kidney tissue were taken to analyze the metabolism and renal function indicators. The single factor analyses of variance (ANOVA) was used to compare differences between groups. The relevant risk factors were analyzed by Pearson correlation test and logistic regression. Results：The weight, and levels of free fatty acids (FFA), fasting glucose (GLU), fasting insulin (FINS), microalbumin (MAU), microalbumin/uric creatinine (ACR), interleukin-1(IL-1), tumor necrosis factor-α(TNF-α), and IL-6 in HF group were higher than those in NF group (P<0.05). The above indexes in HF+LBBR group and HF+HBBR group were lower than those in HF group (P<0.05). Renal pathology revealed kidney damage in HF group, while kidney damage was improved in HF+LBBR and HF+HBBR groups. Pearson correlation analysis showed that ACR was positively correlated with blood glucose (r=0.35), insulin (r=0.82), free fatty acids (r=0.49), IL-1 (r=0.77), TNF-α(r=0.78), and IL-6 (r=0.76, P<0.05). Logistic regression analysis showed that IL-6 was independent risk factor for ACR (OR=1.18, 95% CI 1.03-1.35, P=0.014). In kidney tissue of HF group, the TLR4 and TLR2 expressions were significantly decreased, while nuclear factor-κB (NF-κB) and transforming growth factor-β (TGF-β) expressions were increased (P<0.05), and berberine reversed the changes (P<0.05). Conclusions：The berberine could alleviated kidney damage of high-fat feeding rats, which might be related to berberine increased toll-like receptors (TLR4, TLR2) expressions in kidney tissue.