Objective To study the effect of protein kinase A(PKA) signal transduction pathways on the phosphorylation of cAMP-response element binding protein(CREB) and the expression of peroxisome proliferator-activated receptor-γ coactivator 1α(PGC-1α) in cultured hepatocytes.Methods Primary rat hepatocytes were treated with H89 or H89 plus Foskolin.After that,the expression of CREB and PGC-1α was analyzed by Western blot and RT-PCR.Results Treatment with Foskolin led to increased expression of both phospho-CREB and PGC-1α in the hapatocytes,but resulted in deceased expression of the two proteins in H89 pre-treated cells(P 0.01).Conclusion It is demonstrated that PKA signal transduction pathway may be involved in the glucose metabolism through controlling the expressions of CREB and PGC-1α in liver.