Cellulose nanofibers (CNFs) were isolated from poplar wood by using a mild chemical pretreatment combined with a high-intensity ultrasonication method. The as-prepared CNFs were used as a template to load indomethacin (IMC). With the nucleation and growth of IMC on the surfaces of CNFs and CNF clusters, CNF/IMC composite fibers were eventually fabricated. The effects of solvent and processing method on the structures of the composite fibers were analyzed in terms of morphology, surface charge, and crystal form. Drug-release characteristics of the composite fibers were evaluated by dissolution tests, in which the drug-releasing curves of the composite fibers were fitted to a mathematical model describing the releasing kinetics. The experimental results demonstrated that the composite fibers possessed an encapsulation efficiency of up to 97 %, and a sustained drug-release period of over 30 days.