Objective To examine the potential mechanism of Ling Zhu Tusizi Pills in a rat model of adriamycininduced proteinuria. Methods Thirty-six specific-pathogen-free male SD rats were divided randomly into six groups (n= 6 rats per group), including blank, model, low-dose Ling Zhu Tusizi (14 g / (kg·d)), medium-dose Ling Zhu Tusizi (28g / (kg·d)), high-dose Ling Zhu Tusizi ( 56 g / ( kg·d)), and pyrrolidine dithiocarbamate ( PDTC; nuclear factor-κB inhibitor; 100 mg / (kg·d)) groups. The last five groups also received two injections of adriamycin into the tail vein to develop the nephropathy model, with one dose of 4 mg / kg and another dose of 2 mg / kg given 1 week apart. After successful establishment of the model, Ling Zhu Tusizi Pills were administered for 6 weeks. We examined general vital signs and body weights of the rats, as well as 24 h urine protein, plasma albumin, serum creatinine, blood urea nitrogen, and C-reactive protein. Morphological alterations of the renal tubules and glomeruli, renal fibrosis and basement membrane thickness were observed by hematoxylin and eosin, Masson, and periodic-acid Schiff staining. Modification of the foot process in glomerular podocytes was observed by transmission electron microscopy. Serum levels of pro-inflammatory molecules including interleukin (IL)-6 and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay. I-κB kinase β( IKKβ) / nuclear factor (NF)-κB/ monocyte chemoattractant protein-1 ( MCP-1) pathway-related proteins and nephrin and podocin proteins were detected by Western Blot. Results General health was poorer in the model group compared with the control group, as evidenced by body weight loss, increased 24 h urine protein, and decreased albumin. Renal tubule enlargement, disorganized glomerular visceral cell arrangement, diffuse foot process fusion, podocyte death,extensive fiber deposition, and basement membrane thickening were also noted in the model group. Serum levels of the proinflammatory markers IL-6, TNF-α and CRP were increased, renal-tissue phosphorylated (p)-IKKβ, p-NF-κB and MCP- 1 protein expression levels and the p-IKKβ/ IKKβ and p-NF-κB/ NF-κB ratios were increased, while nephrin and podocin expression levels were decreased ( P< 0. 05 ) in model compared with control rats. Rats in each treatment group experienced variable degrees of symptom relief compared with the model group, with medium-dose Ling Zhu Tusizi Pills having the best therapeutic effect. Rats in this group were generally healthy, with increased body weight and albumin and decreased 24 h urine protein. There were also notable reductions in fibrosis and renal tubule edema, a smooth arrangement of cells in the glomerular visceral layer, enhanced foot process fusion, and no thickening of the basement membrane. Serum levels of IL-6, TNF-α, and CRP were decreased, nephrin and podocin expression were increased, and p-IKKβ, p-NF-κB,MCP-1, p-IKKβ/ IKKβ and p-NF-κB/ NF-κB expression were all significantly decreased in renal tissues in this group (P<0. 05). Conclusions Ling Zhu Tusizi Pills reduced 24 h urine protein and serum pro-inflammatory markers in rats with adriamycin-induced nephropathy, possibly via inhibition of the IKKβ/ NF-κB/ MCP-1 signaling pathway.