AIM:To prepare valaciclovir polybutylcyan_oacrylate nanoparticles (VACV-PBCA-NP) with liver targeting and hepatocyte permeable charateristics.METHODS: Emulsion polymerization method was employed to prepare VACV-PBCA-NP.The formula and preparation conditions were optimized by using the uniform design. The organ distribution of the intravenously injected VACV-PBCA-NP and VACV in animal was determined using HPLC. The hepatocytes permeability of VACV-PBCA-NP was demonstrated by cell uptake experiment in vitro.RESULTS:The drug loading and the drug embedding ratio of VACV-PBCA-NP were 11.20% and 84.85% respectively, with an average diameter of 104.77nm ±11.78nm. The releasing characteristics in vitro fitted the two-phase kinetics. 74.49% of the drug was found to localize in the liver 15min after the administration of VACV-PBCA-NP in the mice. Compared with VACV, VACV-PBCA-NP showed distinct characteristic of sustainedrelease in vivo and the drug entering hepatocytes were also greatly increased.CONCLUSION:VACV-PBCA-NP has the char_acteristic of liver targeting and can increase the permeability of VACV to hepatocytes.