Selective targeting of drugs to kidneys may improve renal effectiveness and reduce extrarenal toxicity. Using fluorescence imaging, we found for the first time that randomly 50% N-acetylated low molecular weight chitosan (LMWC) selectively accumulated in the kidneys, especially in the renal tubules after i.v. injection in mice. To develop and evaluate the novel renal drug carrier, prednisolone, used as a model drug, was covalently coupled with various molecular weight LMWCs via a succinic acid spacer. The mean residence time (MRT) in plasma of prednisolone conjugates increased as the molecular weight increased. The conjugate with molecular weight 19 kD (conjugate-19k) displayed the highest accumulation rate in the kidneys, which was 14.06+/-2.81% of the administered dose 15 min after i.v. injection. The total amount of the conjugate-19k in the kidneys was 13-fold higher than that of controlled prednisolone group. Both conjugate-19k and conjugate-31k had higher retention and about 10% of injected dose was still retained in the kidneys after 120 min. Additionally, MTT assay showed LMWCs were noncytotoxic towards L929 and NRK-52E cells. Conclusion can be drawn that the coupling of prednisolone to the proper molecular weight LMWC results in increased prednisolone concentration in the kidneys. Therefore, LMWC with a proper molecular weight can be applied as a promising carrier for renal targeting.