Objective To investigate the efficacy and safety of low-dose rituximab therapy and sequential maintenance for patients with refractory idiopathic thrombocytopenic purpura. Methods Thirty-three patients with refractory idiopathic thrombocytopenic purpura received intravenous rituximab at the dose of 100 mg once a week for 4 consecutive weeks. Complete blood cell count and serum concentrations of immunoglobulin (IgG,IgM and IgA) were monitored regularly. The numbers of CD3+ and CD19+ CD20+ lymphocyte cells were assayed by flow cytometry before and after therapy. Twenty-five patients with responses(complete response and response) were divided into maintained group (12 patients) and control group (13 patients) by random digits table method. The patients in maintained group were treated with rituximab 100 mg every 6 months. The efficacy of maintenance therapy was evaluated through long-term follow-up. Results The complete response(CR) rate, response (R) rate and no response(NR) rate were 48.48%(16/33), 27.27%(9/33) and 24.24% (8/33), respectively. As a result, total effective rate was 75.76% (25/33). There were no significant changes of peripheral blood white blood cell count,hemoglobin,serum immunoglobulin and CD3+lymphocyte counts before and after treatment (P>0.05). However, CD19+ CD20+ cells were almost depleted in patients treated with rituximab: (3.71±2.64)×106/L vs. (279.33±92.78)×106/L, P<0.01. Five patients suffered from allergic response, and 1 patient developed pneumonia and respiratory failure. The relapse rates of maintained group and control group were 1/12 and 4/13, respectively. Conclusions Treatment with low-dose rituximab may be an effective and safe approach in patients with idiopathic thrombocytopenic purpura. Relapse rates can be decreased through maintenance therapy with refractory low-dose rituximab. However, the optimal therapeutic schedule need further investigation.