OBJECTIVE: This study aims to investigate the therapeutic effects of modified Huangqi Chifeng decoction (MHCD) on proteinuria in membranous nephropathy (MN) and its potential protective effects on podocytes. Furthermore, we explored whether these effects are associated with the inhibition of the nuclear factor kappa-B (NF-κB) pathway. METHODS: Passive Heymann nephritis (PHN) rat model was applied with a single tail vein injection of sheep anti-rat Fx1A serum (0.4 ml/100g). All rats were divided into four groups: normal group, PHN group, benazepril group (10 mg/kg), and MHCD group (12.5 g/kg), and were treated for 6 weeks. 24-hour urine protein levels and serum biochemical parameters were measured. Optical microscopy and transmission electron microscopy were performed to assess pathological changes in renal tissues. Additionally, the expression levels of IgG, C5b-9, nephrin, podocin, Wilms' tumor gene 1 (WT-1), and NF-κB p65 were evaluated. RESULTS: PHN rats exhibited progressive proteinuria over time. However, MHCD treatment significantly reduced levels of proteinuria and triglyceride, while increased levels of albumin. Moreover, MHCD alleviated pathological damage in renal tissues, and reduced the expression of IgG and membrane attack complex (C5b-9). Immunohistochemistry analysis revealed that MHCD increased the expression of nephrin, podocin, and WT-1. Western blot analysis showed that MHCD increased the expression of nephrin and podocin while inhibiting the activation of NF-κB p65. CONCLUSIONS: Our findings indicate that MHCD exert reno-protective effects in the experimental rat model of MN by alleviating podocyte damage and inhibiting the NF-κB pathway.