In this work, a heparin-mimicking polyurethane (HMPU) was synthesized for the modification of polyethersulfone (PES) membranes to improve the blood compatibility by a blending method. Firstly, polyurethane was synthesized using 4,4'-diphenylmethane diisocyanate (MDI) and dimethylolpropionic acid (DMPA), and then sulfonated by concentrated H2SO4 to obtain a heparin-mimicking structure. The PES and modified PES membranes were investigated both in vitro and in vivo. In the in vitro experiments, modified PES flat-sheet membranes were prepared, and the membranes showed decreased protein adsorption, increased clotting time, lowered thrombin-antithrombin III (TAT) generation and suppressed platelet adhesion. In the in vivo experiments, modified PES hollow fiber membrane hemodialyzers were prepared, and Beagle dogs were selected as experimental animals. The reduction ratios of urea and creatinine were about 69% and 68.5% after hemodialysis for 4 h, respectively. These results suggested that the modified PES membranes with good blood compatibility allowed practical application in the field of blood purification. (C) 2014 Elsevier B.V. All rights reserved.