To investigate the hepatic development association with hematopoiesis, a high proliferative potential colony forming cells (HPP-CFC) model of mouse fetal liver was set up. Some differentiational assays based on individual HPP colonies were performed. Under the condition of combinations of hematopoietic and hepatic factors, some individual HPP colonies were induced into hematopoietic and hepatic cells, which were examined with transmission electron microscope (TEM), nested RT-PCR and immunofluorescence staining. The results showed that induced HPP colonies cells with a specific ultrastructure similar to hepatic epithelial cells, expressed hepatic markers including albumin (ALB), α-fetoprotein (AFP), cytokeratins (CK8, CK18) at different extent of percentage. These cells also expressed mesenchymal marker α-SMA and primary endothelial cell marker Flk-1. The MACS results suggested that the fetal liver-derived HPP-CFCs are all from CD45⁺ cells, while CD45^- cells have no capacity to form hematopoietic colony at all. The FACS sorted CD49f⁺/Sca-1⁺ cells have no difference of hepatic differentiation potential compared with whole fetal liver cells. The clonality was confirmed by cell mixing assay. Taken together, the HPP-CFC may represent a novel clonal model for hepatic differentiation from the blood cells in the mouse feta liver and will shed light on the associations underlying the hepatic and hematopoietic development.