The sex steroid hormone estradiol-17β(E2) mediate their biological effects on development, differentiation and maintenance of reproductive tract and other target tissue through gene regulation by nuclear steroid receptors. Although the importance of E2 in many physiological process has been reported, but little is known about the effects of E2 on primary cultured chicken hepatocyte. therefore, in the present study, we have examined the effect of E2 on cell proliferation and it`s related signal cascades. E2 increase [3H]-thymidine incorporation in time-(≤8hr) and dose-(10-10M)dependent manner and treatment of E2 increased the phos-phorylation of p44/43 MAPKs(p44/42 mitogen-activated protein kinase) and JNK(c-Jun N-terminal kinase) in a time dependent manner. In addition, PD98059(p44/42 blocker, 10-5 M), SP600125(JNK blocker, 10-6M) blocked the estrogen-induced increase in [3H]-thymidine incorporation. In conclusion, E2 stimulates the proliferation of primary cultured chicken hepatocytes and this action is mediated by p44/42 MAPKs and JNK signal transduction pathway.