Background: Large yellow croaker (Pseudosciaena crocea) is an economically important marine fish in China suffering from severe outbreaks of infectious disease caused by marine bacteria such as Vibrio and Aeromonas hydrophila, resulting in great economic losses. However, the mechanisms involved in immune response to bacterial infection are far from being fully understood. In order to understand the molecular mechanisms underlying the immune response to such pathogenic bacteria, we used high-throughput deep sequencing technology to investigate the transcriptome and comparative expression profiles of large yellow croaker infected with Aeromonas hydrophila.Results: A total of 13611340 reads were obtained and assembled into 26313 scaffolds in transcriptional responses of the large yellow croaker infected with A. Hydrophila. Annotation to NCBI database, we finally obtained 8260 identified unigenes. 5557 (67％) unigenes were classified into Gene Ontology and 2052 unigenes were found in 23 KEGG categories. These genes included representatives from almost all the functional categories. Using Solexa/Illuminas DGE system, a total of 3010 differentially expressed genes were detected including 1679 upregulated and 1331 downregulated unigenes in comparative analysis of expression profile. Dramatic differences were observed in genes involved in inflammatory response. Bacterial infection affected the gene expression of many components of signaling cascades, including the Toll-like receptor, JAK-STAT, and MAPK pathways. Interestingly, genes encoding factors involved in T cell receptor (TCR) signaling were also revealed to be regulated by infection in these fish. Conclusion: The Based on our results, we conclude that inflammatory response may play an important role in the early stages of infection. The signaling cascades such as the Toll-like receptor, JAK-STAT, and MAPK pathways are regulated by A. Hydrophila infection. Interestingly, genes encoding factors involved in T cell receptor (TCR) signaling were revealed to be down-regulated by infection, indicating that TCR signaling was suppressed at this early period. These results revealed changes of multiple signaling pathways involved in immunity during A. Hydrophila infection, which will facilitate our comprehensive understanding of the mechanisms involved in the immune response to bacterial infection in large yellow croaker.