Abstract: Objective To explore the underlying mechanism of “Gubentongluo Formula” in treatment of IgA nephropathy (IgAN). Methods After the IgAN model was successfully induced at week 12, the Kunming mice were randomly divided into three groups: normal control group (n=15), IgAN group (n=15) and Traditional Chinese Medicine (TCM) group. The mice in normal control and IgAN group were intragastriclly administrated with normal saline for 8 weeks; meanwhile, the mice in TCM group were intragastriclly administrated with “Gubentongluo Formula” 1.35 mL/ (g·d). The levels of 24 h urine protein were determined at Week 0, 12 and 20. At week 20, the changes of renal pathology were detected; the mRNA expressions of transforming growth factor-β (TGF-β) and small mothers against decapentaplegic (Smad) 3 in Peyer’s patches (PPs) were detected by fuorescent quantitative reverse transcription-polymerase chain reaction; the protein expressions of TGF-β and Smad 3 in PPs were detected by immunohistochemistry technique; the levels of (IgA+B)/B lymphocytes in PPs were determined by flow cytometry. Results Compared with those results of normal control group, the levels of 24 h urine protein, IgA deposition in glomerular mesangial area, and expressions of protein and mRNA of TGF-β and Smad3 in IgAN group were significantly increased (P<0.01). Besides, the levels of (IgA+B)/B lymphocytes were significantly elevated in IgAN group (P<0.01). All these indicators were improved in TCM group. Compared with IgAN group, the differences were statistically significant (P<0.01). Compared with those results of control group, the levels of (IgA+B)/B lymphocytes showed no significant difference in TCM group (P>0.05), but other indicators showed significant differences (P<0.01). Conclusion “Gubentongluo Formula” could effectively improve proteinuria and suppress IgA deposition in glomerular mesangial area in IgAN mice, due to affect IgA class switch recombination of B lymphocytes in PPs through regulating TGF-β/Smad3 pathway.