This study was purposed to investigate the changes of serum immunoglobulin (Ig) level during treatment of diffuse large B cell lymphoma by using rituximab (RTX) combined with CHOP. Total of 122 newly diagnosed patients with CD20(+) diffuse large B cell lymphoma from January 2004 to December 2009 were analyzed retrospectively. According to different treatment regimens, 122 patients were divided into 2 group: group treated with CHOP (n = 24) and group treated with R-CHOP (n = 98, out of which 16 patients with abnormal Ig levels before treatment). Ig levels of patients in 2 groups at different stages were recorded and analyzed after abandoning those patients with abnormal Ig levels before treatment. The results showed that after 6 cycles of treatment, among the total 82 patients with normal levels of serum immunoglobulin, the decreased levels of IgG, IgA and IgM by 20% of baseline value were found in 85.4% (70/82), 85.4% (70/82) and 87.8% (72/82) patients respectively, while levels of IgG, IgA and IgM < low limit of normal value were observed in 47.6% (39/82), 48.8% (40/82) and 52.4% (43/82) patients respectively. No obvious changes of IgG, IgA and IgM levels were found in 24 patients of CHOP group before and after treatment.It is concluded that hypogammaglobulinemia is a common complication in chemotherapy using RTX combined with CHOP, the decreased level of Ig is recovered to normal level about 1 year after stop of treatment, the decrease of Ig in some cases can last even for over 2 years.