Inflammation and oxidative stress are critical pathological factors for uremia in dialysis patients. Hemodialysis is recognized as one of the renal replacement therapeutic methods for uremic patients, which can improve the symptoms and prolong their life. The present study was designed to compare the clinical effects of high flux hemodialysis (HFHD) with hemodialysis filtration (HDF) in the treatment of uremia in end-stage renal disease (ESRD) patients, and to explore the possible underlying mechanisms. A total of 56 uremia patients from March 2009 to April 2013 were recruited and randomly assigned to intervention (n=28) and control (n=28) groups. The control group was received only HDF therapy and the intervention group was subjected to HFHD treatment three times a week for 3 months. After 3 months of treatment, the malondialdehyde, (MDA, 4.8+/-1.3 VS. 1.7+/-0.8, P=0.024) and cortisol (Cor, 132.7+/-16.8 VS. 67.5+/-19.4, P=0.031) levels in peripheral blood mononuclear cells (PBMCs) of intervention group reduced more, but the glutathione (GSH, 0.1+/-0.2 VS. 0.3+/-0.2, P=0.024) and super oxide dismutase (SOD, 0.2+/-0.1 VS. 0.4+/-0.6, P=0.031) levels in PBMCs of intervention group decreased less than the control group. In comparison with the control group, the levels of C-reactive protein (CRP, 8.3+/-2.6 VS. 5.1+/-1.7, P=0.012), interleukin-6 (IL-6, 145.2+/-33.5 VS. 95.7+/-21.6, P=0.010) and tumor necrosis factor-alpha (TNF-alpha, 8.4+/-1.8 VS. 5.3+/-1.4, P=0.011) in PBMCs of intervention group were significantly decreased. The patients in the intervention group exhibited a better improvement in quality of life than the control group from baseline to 3 months treatment. Our results demonstrate that HFHD can significantly improve the metabolic disorders in blood lipid, calcium and phosphorus, and effectively inhibit the inflammatory mediums and oxidative stress of PBMCs, which may largely contribute to the improvement in quality of life in uremic patients in a short time. A large number of prospective researches are needed to investigate the long term effects of HFHD and HDF on uremic patients.