To investigate the antiangiogenic effect of sustained-release poly (lactic-co-glycolic acid) microspheres containing docetaxel (PMCD) in human hepatoma xenograft. PMCD were prepared by solvent evaporation method with an encapsulation efficiency of 98.7% and a release period of about 3 weeks in vitro. PMCD were intratumorally injected once for mice bearing a human hepatocellular carcinoma. On day 21 post-treatment, the inhibition rate of tumor growth was 72.7% in the high-dose group, indicating a significant antitumor activity. Meanwhile, excellent antiangiogenic effect was observed based on the contrast-enhanced ultrasonography as well as microvessel density determination. Additionally, the real-time fluorescence quantitative PCR revealed that the expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiopoietin-2 (Ang2) genes were down-regulated significantly. Interstitial chemotherapy using PMCD was highly effective and safe for the treatment of the human hepatoma xenograft and that decreasing angiogenesis could be one of the most important mechanisms involved in the antitumor activity.