Signal Transducer and Activator of Transcription 3 (Stat3) is a latent protein activated in response to various cytokines and growth factors. It is believed that Stat3 is a key signaling molecule involved in the regulation of acute phase gene expression by interleukin 6 in hepatocytes. We report that both IL-6 and interferon γ (IFNγ) up-regulate the expression of Stat3 on both mRNA and protein levels in rat and human hepatoma cells. The effect of IL-6 and IFNγ on Stat3 mRNA expression was time- and dose-dependent. Other factors, including IL-1, TNFα, EGF, Dexamethasone and PMA, did not have any effect on Stat3 mRNA expression. Moreover, we show that the rapid induction of Stat3 expression by IL-6 and IFNγ was independent of ongoing protein synthesis, suggesting regulation by Stat3 and Stat1, respectively.