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Background Liver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicityof the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs arecurrently under hot investigation with great clinical significance. This study was aimed to investigate thedifferent tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the micebody after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in differentdiameters on normal mice liver.Methods One hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in eachgroup (5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycininjection was employed as the control group). A single dose of either conjugated or free adriamycin equaled2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin concentrations in the respectivelycollected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquidchromatography with fluorescence detector.Results Compared with the control group, adriamycin was hardly detected in the heart muscle of the treatmentgroups (P＜0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. Theadriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher thanthat in the control group, except for the group with the nanoparticles diameters of (22.3±6.2) nm (P＜0.05). TheADM-PBCA-NP in (101.0±20.3) nm diameter had the highest liver distribution, and the second highestadriamycin distribution in liver was the group of (143.0±23.5) nm diameter (P＜0.05). Moreover, adriamycinwas released slowly in the liver during the detection period in the experimental groups. ADM-PBCA-NP in (22.3±6.2) nm diameter was not distributed in the tissue of the liver, kidney, heart, spleen, and lung.Conclusions ADM-PBCA-NP in 100-150 nm diameter range has the best liver targeting with a characteristicof slow medicine release. It also decreases the medicine distribution in the heart, kidney and lung. In thetreatment of liver cancer, the polybutylcyanoacrylate nanoparticles system has a good liver targeting ability,which increases the anticancer activity and markedly decreases the toxicity of adriamycin.