Long-circulating drug carriers are highly desirable in drug delivery system.However,nonspecific protein adsorption leaves a great challenge in drug delivery of intravenous administration and significantly affects both the pharmacokinetic profiles of the carrier and drugs,resulting in negatively affect of therapeutic efficiency.Therefore,it is important to make surface modification of drug carriers by protein-resistant materials to prolong the blood circulation time and increase the targeted accumulation of therapeutic agents.In this review,we highlight the possible mechanism of protein resistance and recent progress of the alternative protein-resistant materials and their drug carriers,such as poly(ethylene glycol),oligo(ethylene glycol),zwitterionic materials,and red blood cells adhesion.