To investigate the curative effects of high-dose methylprednisolone (HDMP) in the treatment of refractory chronic lymphocytic leukemia (CLL), 5 patients with CLL who poorly reacted to several cycles of fludarabine based protocols with or without rituximab were treated with 1 to 6 cycles of HDMP with 1 g/(m(2)xd) for d1-5. All the patients were at Binet stage C. 3 patients were at Rai stage IV and 2 were at Rai stage III. 2 patients were diagnosed as Richter syndrome. CD38 and ZAP-70 were expressed in 5 and 3 patients respectively. All the patients developed with B group symptoms including fever, night sweat and/or weight loss and so on. Clinical manifestations and complete blood cell count, peripheral blood smear, bone marrow aspirate, hepatic and renal function, blood serum electrolytes, blood glucose were examined, CD5(+)CD19(+) lymphocytes of peripheral blood and bone marrow were determined by flow cytometry. The results showed that B group symptoms disappeared in 4 patients at 2 - 4 weeks after therapy. The size of enlarged lymph nodes was reduced in all the 5 patients. In 1 patient spleen was not palpable from 10 cm below costal margin at 2 weeks after therapy, and his hemafecia was alleviated. The renal function in another patient with renal failure recovered to normal after two cycles of therapy. Pancytopenia improved in 3 patients after therapy. CD5(+)CD19(+) lymphocytes decreased in all the patients. 4 patients acquired partial remission and 1 patient acquired stable status of disease. The side effects became mild. In conclusion, the therapeutic results preliminarily show that HDMP is an effective and safe protocol for the treatment of refractory CLL.