Abstract: OBJECTIVE To investigate the tissues distribution and anti-tumor pharmacodynamics of monostearin solid lipid nanoparticles (SLN) and SLN modified by PEG2000-SA (pSLN) in vivo of mice. METHODS The SLN was prepared by aqueous solvent diffusion method, subsequently modified with PEG2000-SA as hydrophilic groups. The particle diameters, Zeta potentials, surface element, contact angle and stability of SLN and pSLN were determined. Tissues distributions of SLN and pSLN preparations in vivo of rats after oral administration were determined and the determining results were calculated with DiR as fluorescent marker. The in vivo antitumor efficacy and safety of the DOX-loaded nanoparticles was evaluated using BEL-7402 bearing mice model after oral administration. RESULTS The size of pSLN was smaller than that of SLN after modified by PEG. The Zeta potential of pSLN was about -20 mV and the surface hydrophilicity was improved after PEGylation of SLN. The pSLN accumulated in the tumor tissues and liver after oral administration, and the residence time in the tissue of nanoparticles was significantly prolonged after modified by PEG-SA. Furthermore, in vivo studies indicated that pSLN as a nanocarrier for the oral drug delivery system conducted well in maintaining therapeutic effects and inhibiting the growth of the solid tumor while reducing the toxicity against animal body. CONCLUSION Oral delivery of SLN can improve bio-distribution in vivo after modification with PEG-SA while reducing toxicity to normal tissue.