Objective ·To evaluate clinical efficacy and safety of rituximab (RTX) in the patients with refractory primary membranous nephropathy (PMN). Methods ·A retrospective analysis was carried out on the patients with refractory PMN, who had recurred or had not achieved clinical remission after more than 1 year of treatment with glucocorticoid and cyclosporine, cyclophosphamide or tacrolimus, admitted to the Department of Nephrology, Qingpu Branch of Zhongshan Hospital, Fudan University from July 2018 to April 2022. They received 2 doses of RTX. The single dose of RTX was 1 000 mg, and the interval between the two doses was 2 weeks. After 6 months, the numbers of peripheral blood B cells of the patients were detected. If the count of peripheral blood B cells were greater than 5 cell/μL, another 1 000 mg RTX would be added. The main indicators were serum albumin, serum creatinine, urinary protein/creatinine ratio (UPCR), blood antibody against phospholipase A2 receptor (PLA2R) antibody, peripheral blood B cell count, and serum total IgG level. The clinical efficacy and safety of the treatment regimen were evaluated by observing the change of the main indicators of patients and adverse reactions. Results ·A total of 18 patients were included, with an average age of (58.17±16.73) years, including 11 males. The total dose of RTX was (2 222.22±485.07) mg, and the follow-up time after RTX treatment was (14.9±4.9) months. At the last follow-up, the serum albumin level was significantly higher than that before RTX treatment [(36.50±5.33) g/L vs (27.61±8.59) g/L, P=0.009]; the serum creatinine level was stable (P>0.05); the value of UPCR decreased significantly [863.30 (203.20, 2 291.75) mg/g vs 2 954.00 (1 458.00, 7 260.75) mg/g, P=0.047]; the PLA2R antibody decreased significantly [(44.32±33.71) RU/mL vs (168.40±88.40) RU/mL, P=0.015]; the peripheral blood B cell count decreased significantly [(37.89±12.43) cell/μL vs (246.40±239.98) cell/μL, P=0.009]; the total blood IgG level was stable (P>0.05). After RTX treatment, 8 patients achieved complete remission (44.4%), 7 patients achieved partial remission (38.9%), and the overall effective rate was 83.3%; only 3 patients were unrelieved (16.7%). In terms of adverse reactions, 1 patient had transfusion allergy reaction, and 1 patient had pulmonary infection. Conclusion ·For the patients with refractory PMN who have relapse or do not relieve after traditional immunosuppressive therapy, RTX treatment can effectively induce clinically complete remission or partial remission with good safety.