Human activin A is a homodimer of βA subunit which is synthesized in the form of prepro-activin with 426 amino acids; mature activin A with 116 amino acids is processed from this larger precursor protein. This protein which was extracted for the first time from follicular fluid is a strong stimulator of FSH biosynthesis. The functions have been found to be exerted by activin, including roles in cell proliferation, differentiation, apoptosis and survival of neurons. As this protein plays a considerable role in the treatment of neurodegenerative disease such as Alzheimer,s disease and wound repair, in this study for the first time was expressed in three different strains of E.coli. Activin A has disulfide bonds in its native and functional structure, so the cytoplasmic reducing environment of E.coli is not appropriate for its expression. Therefore, the oxidative space of periplasm for production of correctly folded activin A was considered. In this study, h-activin A cDNA and modified Iranian Bacillus Licheniformis α-amylase signal peptide obtained from NCBI data bank after codon optimization was cloned in pET21b(+) vector and transformed to BL21(DE3)pLysS, BL21(DE3)Rosetta gami and BL21(DE3) strains of E.coli. Expression occurred via induction of promoter with IPTG. Consequently, extracted proteins from these three strains were compared with each other using SDS-PAGE, Dot blot and western blot techniques. The data shows activin A expression especially in BL21(DE3) and BL21(DE3)Rosetta gami strains of E.coli.