The study was purposed to explore the changes of CD4(+)CD25(+) T regulatory cells in patients with multiple myeloma before and (MM) after treatment with thalidomide so as to provide evidences for effective immunotherapy. The population of CD3(+) T, CD4(+) T, CD8(+) T, NK and CD4(+)CD25(+) Treg in patients with MM were detected by flow cytometry. Statistical significance of differences in different groups was determined by using the t test. A p value of less than 0.05 was considered to be significant. The results showed that the percentage of CD4(+)CD25(+ high) T in patients with MM was significantly higher than that of the healthy donors (p > 0.01). The population of CD4(+)CD25(+ high) Treg cells in patients with response to thalidomide was significantly decreased (p < 0.01), but the population of these cells in patients without response not changed significantly (p > 0.05), as compared with patients before treatment. In 16 patients who achieved complete remission after chemotherapy, the population of CD4(+)CD25(+ high) T was 6.91 +/- 1.12%, which was slightly higher than that before treatment. The population of CD3(+) T, CD4(+) T, CD8(+) T, NK and CD4(+)CD25(+) Treg significantly increased in patients with positive response to thalidomide, but the population of CD8(+) T remained unchanged. It is concluded that the significant increase of CD4(+)CD25(+) regulatory T cells in peripheral blood of patients with MM is concerned with the MM pathogenesis; thalidomide may exert its anti-MM effects by down-regulating CD4(+)CD25(+) Treg.