Abstract: Objective To investigate the clinical outcome of 489 patients with diffuse large B-cell lymphoma (DLBCL), and to identify factors associated with the clinical outcome. Methods Medical records of 489 DLBCL patients admitted to the West China Hospital of Sichuan University from Jan 2000 to Dec 2010 were retrospectively reviewed. The patients were divided into CHOP and RCHOP (rituximab plus CHOP) groups depending on their chemotherapy regimens. The clinical outcomes of the two groups of patients were compared. Results The RCHOP group had a higher response rate than the CHOP group (84.3% vs. 75.6%, P=0.015). The multivariate analysis showed that splenomegaly, low absolute lymphocyte count (ALC), high IPI scores, and CHOP was associate with the low overall-response rate. In the CHOP group, low ALC (OR=2.060，95%CI：1.159-3.661,P=0.014) and high IPI scores (OR=2.157，95%CI：1.170-3.978,P=0.014) were associate with low response rate. In the RCHOP group, anemia (OR=3.010，95%CI：1.238-7.314,P=0.015) and high IPI scores (OR=2.872，95%CI：1.193-6.914,P=0.019) were associate with low response rate. For patients with 0.8×10 9/sup>/L-1.0×10 9/sup>/L ALC, RCHOP therapy was more effective than CHOP. The expression of Bcl-2 and the phenotype of immuno-classification (GCB/non-GCB) were not associated with the difference of overall response rate between the CHOP and RCHOP groups. Conclusion RCHOP therapy increases the overall response rate compared with CHOP alone. Low ALC and anemia is associate with low response rate to CHOP and RCHOP therapy, respectively.