Objective To investigate the effect of EPO on RBC immunity, humoral and cellular immunity and fluidity of RBC membrane in patients with chronic renal failure（CRF）. Methods Sixty-nine patients with CRF were divided into three groups. Group A patients accepted hemodialysis and were treated with EPO. Group B patients were treated with EPO and didn't accept hemodialysis. Group C patients didn't accept EPO treatment and hemodialysis. After 8 weeks treatment, RBC immune functional parameters were detected by the modified Gao's methods; the subpopulations of T lymphocyte were analyzed with APAAP method; Immunoglobulins were measured with radio-immuno, assay (RIA) and RBC membrane fluidity was determined by fluorescence spectrophotometer method. In addition, the infection rate of patients with CRF in different group was compared. Results The parameters of immune functions of patients with CRF were comparable between groups before treatment. After treated with EPO for 8 weeks, RBC numbers and Hb level were significantly increased in patients of group A and Group B, but not in patients of group C. C3b, RFER, IgG and IgA were increased in patients of groups A and groups B and had statistic differences as compared with that in patients of group C (P<0.01). The number of CD3 and CD4 subpopulations, but not CD8 subpopulation were also increased and CD4/CD8 ratio was raised in patients of group A and group B. These parameter changes between either group A or group B and group C have statistic differences. The infection rate was decreased in patients of group A and group B and the difference of infection rate between either group A or group B and group C has statistic significance. Conclusion These results indicated that EPO treatment in patient with CRF significantly modified patients' immune functions and decreased patients' infection rate.