Fluorescent organic nanoparticles (FONs) with aggregation-induced emission (AIE) features have recently emerged as promising fluorescent probes for biomedical applications owing to their excellent optical properties, designability and biocompatibility. Significant progress has been made recently for synthesis and biomedical applications of these AIE-active FONs. However, only very limited reports have demonstrated the fabrication of biodegradable AIE-active FONs with red fluorescence emission. In this study, a novel strategy has been developed for the preparation of biodegradable AIE-active polyurethanes (PUs) through a two-step polymerization, in which the diisocyanate-terminated polyethylene glycol (NCO-PEG-NCO) was synthesized and subsequently conjugated with diamine-containing AIE dye (NH2-Phe-NH2). The successful synthesis of AIE-active Phe-PEG(2000) PUs is evidenced by a series of characterization techniques. Because of the formation of AIE-active amphiphilic PUs, the final copolymers can self assemble into spherical nanoparticles, which exhibit strong luminescence and high water dispersion. The biological evaluation results suggest that the AIE-active Phe-PEG(2000) FONs possess low toxicity and desirable cell permeability. Therefore, we anticipate that these AIE-active FONs with biodegradable potential will trigger much research enthusiasm and effort toward the creation of new AIE-active materials with improved properties for various biomedical applications. (C) 2017 Elsevier Inc. All rights reserved.