Objectives To explore the effect of ultrapure dialysate on Erythropoietin (EPO) hypo - responsiveness or EPO resistance in patients on maintenance hemodialysis dialysis (MHD).Methods 70 patients taking regular hemodialysis were randomly divided into two goups: conventional dialysate group (CD n = 35 ), ultrapure dialysate group( UPD n =35), they all had been on hemodialysis for more than 3 months and on erythropoietin (EPO) ≥100 IU/kg per week for more than 3 months. The dose of EPO was titrated to maintain a target Hct level between 33% and 36%. EPO resistance index (ERI) was calculated as weekly EPO dose per kg of body weight, divided by the Hb concentration (weekly EPO dose/kg weight/g Hb).Laboratory tests include general examination of blood, biochemistry test of blood, serum ferritin, C reactive protein (CRP), normalized protein catabolic rate (nPCR) and intact parathyroid hormone (iPTH) were detected on each patieesnts. The relationship between ERI and laboratory factors mentioned above were analysed. And after 12 - month treatment, difference of hs - CRP and ERI were researched between the two groups. Results Multiple stepwise linear regression analysis showed that CRP was the most important independent predictor of EPO hypo - responsiveness ( R2 = 0.699, p＜0.001). Marked difference of hs -CRP and ERI existed between CD group and UPD group (5.12±2.74 vs 3.77±2.19 p＜0.05 and 16.42±7.05 vs 11. 06±5.27, p＜0.01 respectively). Conclusions CRP is the most important independent predictor of EPO hypo - responsiveness. Use of UPD should be beneficial to the inflammation status and ERI in long- term hemodialysis patients.