Considering their potential for multilineage development and illimitable proliferation potential, embryonic stem (ES) cells may enable cell transplantation therapy. Fair et al. [12] reported that injecting mouse ES cells into the livers of hemophilia B mice corrected FIX deficiency. However, there have been few reports describing cell therapy for hemophilia A using ES cells. Previously, we established mouse Ainv18 ES cells (tet-226aa/N6-Ainv18), which secrete human FVIII (hFVIII) by introducing the human F8 gene [13]. Here, we investigated ES-cell transplantation therapy against hemophilia A.