AIM: To explore the efficacy and safety of two drugs in diagnosed idiopathic membranous nephropathy (IMN). METHODS: A retrospective study was conducted on 113 patients diagnosed with IMN by renal biopsy or PLA2R antibody positive at the department of nephrology, yijishan hospital, wannan medical college from november 2019 to July 2024, of whom 55 received cyclophosphamide treatment and 58 received rituximab treatment, and follow-up was ≥6 months. RESULTS: At 6 months, 38 patients (69.09%) in the cyclophosphamide treatment group and 36 patients (62.07%) in the rituximab treatment group had achieved a combined response (complete or partial response). At 12 and 18 months, there was no statistical difference in the combined response rate between the two groups (70.83% vs. 83.87%, P=0.186 and 73.68% vs. 73.68%, P=1.000), but at 12 months, the combined response rate in the rituximab group was higher than that in the cyclophosphamide group. In IMN patients with eGFR<60 mL/（min·1.73 m2）, rituximab significantly improved renal function (P=0.008). Over the entire follow-up period, the total number of adverse events was higher in the cyclophosphamide group than in the rituximab group (57 vs.. 45), and the incidence of non-serious adverse events was higher than in the rituximab group (P=0.039). CONCLUSION:The efficacy of rituximab in the treatment of IMN is not inferior to that of cyclophosphamide, and it has better safety. Rituximab improved renal function better than cyclophosphamide in patients with eGFR<60 mL/（min·1.73 m2） IMN.