Abstract: Objective To investigate the expression and significance of follistatin, activin A and bone morphogenetic protein-4 (BMP-4) in normal brain tissues of rats and the brain tissues with hypoxic and ischemicgin. Methods Sixty conception SD rats were divided into normal and model group (with 30 for each). According to the development of fetal rats in each group, they were randomly divided into six subgroups (embryonic stage 8.5 d, 13 d, 18 d (E8.5,E13,E18), and after the birth 3 d, 7 d and 30 d (P3,P7,P30), five fetal or young rats in each subgroup. Hypoxic-ischemic brain model was established. Expressions and origins of follistatin, activin A and BMP-4 with hypoxic-ischemic brain damage were determined by immunohistochemical and RT-PCR methods. Results In normal group, follistatin and activin A protein expressed at a very low level and gradually decreased with the period of fetal development when evaluated with immunohistochemical and RT-PCR methods; almost no expression of BMP-4 was detected in embryonic but a little bit of expression at 30 d after the birth. In hypoxic-ischemic brain damage group, the expression of follistatin, activin A and BMP-4 was significantly higher than those in normal group (P<0.01). Conclusion The expression of Follistatin, activin A and BMP-4 are related to developmental time, the expression of follistatin, activin A and BMP-4 is highly increased after cerebral ischemia and hypoxia injury. This implies that the main function of follistatin is as the inhibitor of activin A instead of the ligland of BMP-4 to regulate neural development.