【Abstract】Anemia is a common complication of chronic kidney disease (CKD). Erythropoietin (EPO) significantly improves the anemia status of CKD patients. However, about 5～10% of the patients failed to reach the required hemoglobin level despite the use of a large dose of EPO, which is clinically considered to have low responsiveness to erythropoietin stimulating agent (ESA). According to the recent understanding, iron deficiency, inflammation and infection, severe secondary hyperparathyroidism, inadequate dialysis, antigen-mediated pure erythrocyte aplastic anemia, are the complications leading to low responsiveness to ESA. Clinically, regular diagnostic processes should be conducted to find out the cause of this disease situation and the appropriate management.