In this manuscript, the effect of the particle size of polymer-functionalized mesoporous carbon (MPP) nanoparticles on enhancing oral absorption of a water-insoluble drug is first investigated. The insoluble drug, fenofibrate (Fen), was selected as the model drug loaded in the MPP nanoparticles. MPP nanoparticles with different particle sizes were designed for improving the oral bioavailability of drugs, in which the branched polyethyleneimine (PEI) and polyacrylic acid (PAA) were modified on the surfaces of mesoporous carbon nanoparticles (MCNs) with amide bonds. In addition, PEI-functionalized carbon quantum dots (PCA) and radioisotope I-125 were applied to label the MPP nanoparticles to trace in the vivo process. According to the data, the MPP nanoparticles could markedly improve the dissolution rate and oral bioavailability of Fen. Interestingly, the MPP nanoparticle size had a notable effect on Fen oral absorption, and intermediate sized MPP nanoparticles were expected to be more ideal oral drug carriers. The nanoparticles were safe and easily excreted. These findings present the prospect of MPP nanoparticles for oral application, and guides the rational design of an oral delivery system with respect to particle size. (C) 2017 Elsevier Inc. All rights reserved.