In this work, a water-insoluble β-D-glucan (PCSG), isolated from Poria cocos, was carboxymethylated to create a water-soluble derivative named as CP. After free amino groups have been introduced, CP was covalently immobilized onto PU surface. The hydrophilicity and the concentration of carboxyl group on the modified PU surface were determined. The fibrinogen and albumin adsorption to the surface, in vitro blood compatibility, and antibacterial activity of the surface against Pseudomonas aeruginosa were evaluated. The water contact angle measurement indicated that the hydrophilicity of PU surface increased after modification. The fibrinogen adsorption of the modified PU surface decreased 51.5%, compared with control PU. CP immobilization could prolong the blood coagulation time was suggested by APTT experiment. Antibacterial activity experiments indicated that CP modified surface obviously suppressed the growth of P. aeruginosa. Thereby, CP immobilization improves blood compatibility of PU surface and introduces special antibacterial bioactivity.