Objective To further explore the mechanism by which bone morphogenetic protein 4（BMP-4）might be involved in hematopoietic differentiation of the yolk sac. We observed the expression of BMP-4,CD34, CD133 and tyrosine kinase receptors（KDR） in the blood island of the yolk sac at embryonic 3 to 8 weeks. Methods Gene expression was analyzed by RT-PCR and the presence of BMP-4, CD34, CD133 and KDR proteins was confirmed by immunohistochemistry in 57 human embryos. Results In the human yolk sac, we found that BMP-4 was expressed at high levels from the 16th day to the 7th week, and decreased quickly after week 7 The results showed that KDR, CD133 and CD34 largely appeared on the 21st and 30th day, then increased at the 6th week, and decreased quickly after week 7. Furthermore, Ihh，SCl, GATA-1, GATA-2 and PU.1 mRNAs showed that PU.1 was not expressed on the 16th day; however, other factors were expressed all the time. Conclusion The distribution of BMP-4,KDR,CD34,CD133 and transcription factors expression highly suggested that BMP-4 was secreted from the yolk sac which might exert its effects on the specification of human hemangioblast and hematopoietic ste