Introduction: Some patients with idiopathic membranous nephropathy (iMN) do not respond to cyclophosphamide plus steroids treatment, and we define them as non-responsive iMN. The combined regimen of rituximab (RTX) and tacrolimus (TAC) has an excellent effect on this kind of non-responsive iMN patients; however, the optimal dose is still unclear. In this retrospective study, we comapred the efficacy and safety of ultra-low dose RTX plus low-dose TAC therapy versus standard TAC monotherapy in patients with non-responsive iMN. Materials and methods: Sixty-seven Chinese non-responsive iMN patients were included. There were 41 patients received standard tacrolimus monotherapy (TAC) and 26 patients received ultra-low dose rituximab plus low dose tacrolimus (RTX/TAC) combination therapy. All patients were observed for 12 months. Results: 18 patients (18/26, 69.2%) in the RTX/TAC group and 17 patients (17/41, 41.5%) in the TAC group achieved clinical response after 12-month follow-up (P=0.044). The median time for achieving response in the two groups was 3.0 months. As indicated by Kaplan-Meier curve, the response rate in the RTX/TAC group was higher than that in the TAC group (P=0.015). 24-hour proteinuria, serum albumin, estimated glomerular filtration rate (eGFR) and serum creatinine in the two groups were comparable at baseline; howerver, after 12-month follow up, they were significantly improved in the RTX/TAC group compared with the TAC group (P<0.05). B-cell depletion was achieved in all patients in the RTX/TAC group during the whole follow-up period. Pneumonia, urinary tract infections and glucose intolerance were the major side effects observed in this study. All adverse events were mild, and the cumulative incidence was lower in the RTX/TAC group compared with that in the TAC group (9 (34.6%) vs 27 (65.9%), P=0.023). Conclusion: The combination of ultra-low dose rituximab and low dose tacrolimus is more effective in inducing proteinuria response, improving eGFR and serum albumin in non-responsive iMN patients than standard tacrolimus monotherapy. The combined treatment also has higher safty.