Objective To investigate protein kinase A (PKA) signal regulatory mechanism of corticotropin-releasing hormone (CRH) mRNA expression, after CRH stimulated neuron of hypothalamic slices in rats in vitro. Methods After CRH stimulated corticotropin-releasing hormone type 1 receptor (CRH1R) of hypothalamic slices in rats in vitro, the changes of activity of PKA signal pathway and their relationship with CRH mRNA expression were observed by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting. Results CRH may cause the remarkable increase in phosphorylated PKA (P-PKA), phosphorylated cyclic adenosine monophosphate response element-binding protein (P-CREB) and CRH mRNA content in hypothalamic slices in rats. However, CP-l54526 or H89 could have significant inhibition effects on the synthesis of P-PKA, P-CREB and CRH. Conclusion PKA signal pathway in ultrashort positive feedback control of CRH secretion in hypothalamus in the stress due to severe traumas.