【Abstract】Objective To explore the clinical efficacy of hemodiafiltration on peripheral neuropathy in uremic patients. Methods Sixty- nine maintenance hemodialysis patients complicated with peripheral neurological impairment were randomly assigned to the control group (n=35) in which patients were treated with conventional hemodialysis (HD), or the observation group (n=34) in which patients were treated with hemodiafiltration (HDF). The symptoms of peripheral neuropathy, sensory nerve conduction velocity (SCV), and serum leptin, β2-microglobulin (β2-MG) and parathyroid hormone (PTH) were observed before and after treatment, and the clinical effects were then compared between the two groups. Results The effectiveness rate of peripheral neuropathy symptoms, including disappearance or improvement of the symptoms, was 91.18% in the observation group and 28.57% in the control group (χ2=16.793, P=0.019). After the treatment, serum leptin, β2-MG and PTH were significantly lower in the observation group than in the control group (t=5.374, 9.605 and 8.327 respectively; P＜0.001, 0.001 and＜0.001 respectively). Correlation analyses showed that β2- MG was negatively correlated with tibial nerve SCV and common peroneal nerve SCV (r=-0.789 and -0.832 respectively; P=0.015 and P=0.004 respectively); leptin was negatively correlated with tibial nerve SCV and common peroneal nerve SCV (r=-0.819 and -0.867 respectively; P=0.006 and P＜0.001 respectively); PTH had no significant correlation with tibial nerve SCV and common peroneal nerve SCV (r=-0.327 and -0.359 respectively;P=0.119 and P=0.087 respectively). Conclusion Hemodiafiltration can effectively reduce leptin, β2-MG and PTH levels and improve peripheral neuropathy in uremic patients.