Background: Obese subjects have been considered to be in a state of chronic, low-grade systemic inflammation. Excess fat accumulation and persistent inflammation may promote renal dysfunction, to cause chronic kidney disease (CKD) and even end-stage kidney failure. Coptidis Rhizoma is a classical traditional Chinese herb well known for its hypoglycemic and hypolipidemic properties. The mechanism is partially associated with its anti-inflammatory effect. However, this effect is rarely investigated in obesity and obesity-related glomerulopathy (ORG). Purpose: The current study was designed to evaluate the effect of Coptidis Rhizoma on ORG. It also aimed to determine whether this renal protection effect of Coptidis Rhizoma was related to the inhibition of NLRP3 inflammasome in ORG. Methods: Coptidis Rhizoma concentrated granules were prepared and the main components were identified by 3D-High Performance Liquid Chromatography (3D-HPLC) assay. The animal model of early stage ORG was established in obesity-prone (OP) rats by high protein and high fat diet feeding for 12 weeks. The treatment with Coptidis Rhizoma at different dosages was administered by intragastric infusion simultaneously. Then body weight, kidney weight, plasma lipid profiles, 24 h urine protein/albumin content and kidney histology were measured. Inflammatory biomarkers were examined both in the rat plasma and renal cortex. The gene expressions of NLRP3 inflammasome complex and NF-kappa B in renal tissues were also measured. Results: Coptidis Rhizoma alleviated dyslipidemia and reduced the renal weight of the rats with ORG. Meanwhile, urinary albumin to creatinine ratio and creatinine clearance rate were significantly improved. Coptidis Rhizoma also attenuated glomerular hypertrophy, mesangial hyperplasia, and effacement of podocyte foot in renal tissues of ORG rats. In addition, Coptidis Rhizoma intervention decreased the levels of proinflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, and IL-18) both in plasma and renal tissue. The gene expression of NLRP3 inflammasome was down-regulated and NF-kappa B activity was also inhibited by Coptidis Rhizoma in renal tissues of ORG rats. Conclusion: Coptidis Rhizoma can ameliorate early renal damage in ORG rats and the mechanisms appear to be related to the inhibition of NLRP3 inflammasome complex.