Background: We have previously reported that reduced erythropoietin(Epo) responsiveness to anemia could explain the anemia in diabetic patients before advanced diabetic nephropathy. Thus, the aim of this randomized prospective study is to investigate the therapeutic effect of recombinant human erythropoietin(rHuEpo) on anemia with Epo deficiency in early diabetic nephropathy. Methods: Twenty-nine diabetic patients with the normocytic normochromic anemia of Epo deficiency were randomized into Epo-treatment group(n=20, M:F= 8:12, mean age=52.9±9.2) and control group(n=9, M:F=4:5, mean age=53.6±12.4). Twenty patients of Epo-treatment group were treated with rHuEpo(Epokine (CheilJedang Co.) 4,000unit/day SC., 3 times/week) for 8 weeks. The Epo- treatment group were divided into the responder or non-responder. Patients with increments in Hemoglobin (Hb) during the follow-up duration was above 2g/dL, or with the final Hb was above 14g/dL in men or 13g/dL in women were decided the responder. In order to analyze factors affecting the therapeutic effects of rHuEpo, the clinical and biochemical characteristics were compared between the responder and non-responder group. Results: There was no difference in the clinical and biochemical characteristics between the Epo-treatment and the control group at randomization. The responder group(n=14) had significant increments in Hb, compared to the non-responder group(n=6) or the control group(13.6±1.0 vs. 10.1±1.5 vs 11.2±1.2g/dL, p < 0.001, respectively). The treatment duration of rHuEpo in the responder group was 4.9±2.3 weeks. Among the Epo-treatment group, there was no differences between the responder and the non-responder group in sex, age, duration of diabetes, serum creatinine level, 24 hour urinary albumin excretion rates, HbA1C, frequency or severity of microangiopathy, and serum Epo level. However, the responder group had higher serum ferritin(240.3±108.4 vs 25.8±3.0 ㎍/L, p<0.05) and transferin saturation level(32.7±7.9 vs 21.2±5.3 %, p<0.05). Conclusion: These results concluded that the administration of rHuEpo could be useful in treating anemia with Epo deficiency in early diabetic nephropathy and that the degree of iron storage and functional iron deficiency might affect the therapeutic effects of rHuEpo on this type of anemia(J Kor Diabetes Asso 25:364∼373, 2001).