Background: The Chinese herbal formula Qilong-Lishui granule (QLG) is an effective natural product for treatment of renal disorder. It was composed of six Chinese herbs according to our clinical practice in the treatment of patients with kidney disease. However, molecular and cellular mechanisms of QLG are still unclear. Therefore, the objective of the current study is to investigate molecular and cellular mechanisms of QLG in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. Method: Wistar rats were divided into six groups of sham operation, PAN model, PAN model with high-dosage QLG (QLG-H), PAN model with median-dosage QLG (QLG-M), PAN model with low-dosage QLG (QLG-L), and PAN model with fosinopril (FP). The PAN model was induced by jugular vein injection of PAN at a dose of 5 mg/100 g body weight. Quantities of 24 h urinary protein excretion were examined on days 5, 10, 15, 20, 25 and 30. All rats were sacrificed on day 31 for blood biochemistry, kidney histology and reverse transcriptase-polymerase chain reaction analysis. Results: PAN-induced nephrotic syndrome was successfully produced in rats. Treatment of QLG significantly reduced protein excretion and blood urea nitrogen and creatinine. QLG and FP treatments also improved protein content in blood, and reduced total cholesterol and triglyceride in blood. Moreover, QLG and FP improved the damage of interstitial induced by PAN. Furthermore, CYP and FP were able to reverse BMPRII and Smad1 mRNAs abundance caused by PAN. Conclusion: QLG attenuates PAN-induced kidney injury possibly through the bone morphogenetic protein signal transduction pathway.