Membranous nephropathy (MN) is the predominant cause of primary nephrotic syndrome (NS) among adults. The identification of PLA2R as target antigen has brought about a profound transformation in the management of MN, offering a basis for the utilization of B-cell depleting agents such as rituximab (RTX). The question of whether early intervention targeting antibodies can effectively impede the progression of MN, contributing to enhanced disease control and long-term renal outcomes for patients, remains further exploration. We analyzed demographic data, laboratory parameters, and renal involvement in 13 patients with PLA2R antibody-related MN who received at least one RTX treatment at our center from October 2019 to March 2023. Early-stage medium-to-high-risk MN was defined as baseline or admission anti-PLA2R antibody levels exceeding 50 RU/mL, excluding patients who already presented with nephrotic syndrome at baseline. The median duration of MN at the initiation of the first RTX treatment was 4.1 months (IQR 1-7.7), and the median follow-up time after RTX therapy was 27 months (IQR 23-45). All patients had commenced renin-angiotensin system inhibitors before receiving RTX. Following RTX therapy, none of the 13 patients progressed to NS during the follow-up period, and 12 patients achieved complete or partial remission at the 2-year follow-up or the last visit. No deaths, severe infections, or other serious adverse reactions occurred during the follow-up period. In conclusion, RTX demonstrates favorable efficacy and safety in early-stage, medium-to-high-risk MN patients. Initiating antibody clearance therapy in these patients may be beneficial for long-term disease control and distant renal outcomes.