We investigated a fixed scheme of combination chemotherapy protocol including CHOP, granulocyte colony stimulating factor (G-CSF) and rituximab (CHOP-GR) for patients with diffuse large B cell lymphoma (DLBCL) in a phase II clinical trial. Forty-four patients were registered: 21 patients <61 years of age in the low or low-intermediate International Prognostic Index (IPI) risk group and 23 patients between 61 and 70 years of age in any IPI risk group. The patients underwent two courses of CHOP chemotherapy followed by four courses of CHOP-GR, including subcutaneous G-CSF on days 11-14 and rituximab on day 15. An additional two courses of weekly rituximab were administered. Of the assessable 43 patients, complete remission occurred in 39 (91 %), partial remission in one (2 %), and progressive disease in three (7 %). In the median 53-month observation period in alive patients, the 5-year overall survival rate of the 43 patients was 77 % and the 5-year progression-free survival rate was 69 % with a subsequent plateau. There were nine deaths in the 43 patients, all of which were attributable to lymphoma progression. The most frequent adverse events were leukocytopenia (98 %), neutropenia (94 %), lymphocytopenia (91 %), and alopecia (83 %). CHOP-GR is a safe and effective therapy for patients with untreated DLBCL.