CD41 (αIIb integrin), a specific marker for megakaryocytes and platelets, was recently shown to mark the initiation of definitive hematopoiesis in mouse embryos. However, whether embryonic CD41(+) populations have a nonhematopoietic potential remains elusive. Here, we report that the CD41(+) cells from the mouse E11.0 aorta-gonad-mesonephros (AGM) region and yolk sac (YS) expressed a set of mesenchymal markers (as revealed by reverse transcriptase-polymerase chain reaction), displayed myofibroblastic/fibroblastic potential in vitro under mesenchymal culture conditions, and differentiated into α-SMA(+)/epimorphin(+)/vimentin(+) cells in the lungs of adult recipients after systemic transplantation. This unique cell population with fibroblastic potential expressed intermediate rather than high levels of CD41 and was negative for CD34 in the AGM region. In contrast, circulating CD41(+) cells in the embryonic blood stream harbored no similar fibroblastic potential. Compared with the YS, the AGM-derived CD41(+) cells had a more robust fibroblastic potential, as revealed by higher in vitro growth rates. Interestingly, the AGM-derived CD41(+) cells demonstrated a stronger response to the chemotaxin of circulating blood plasma than the YS-derived CD41(+) cells. We are the first group that illustrates the fibroblastic potential of an embryonic CD41(+) population in vitro and in vivo, reflecting the close association between blood and mesenchyme development during mouse mid-gestation. The precise origin of these mesenchymal populations needs further clarification.