Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. Since insulin-like growth factor II (IGF-II) has been reported to play a significant role in liver regeneration and hepatocarcinogenesis, we initially examined its angiogenic effect on the chorioallantoic membrane (CAM) of 9-day-old chick embryos. We also investigated whether IGF-II secreted from HepG2 human hepatocellular carcinoma cells induces vascularization using the chick embryo CAM. We found that the concentrated conditioned media (CCM) of HepG2 cell culture induced angiogenesis on the CAM. We also identified IGF-II protein in the CCM from HepG2 cells by Western blot analysis. However, CCM from Chang liver cells, which are normal human liver cells and were free of IGF-II, did not induce angiogenesis in the CAM. These results suggest that IGF-II secreted from hepatocellular carcinoma cells may act as an angiogenic factor for the hypervascularization of HCC.