Murine typhus is a febrile disease caused by the bacterium, Rickettsia typhi (R. typhi), and transmitted via infected fleas. This study investigated midgut responses of infected versus uninfected cat fleas (Ctenocephalides felis) by constructing cDNA libraries and examining transcript levels. Select C. felis serine proteases, GTPases and defense response genes were compared to identify differences in gene expression between the two states of infection. A total of 1152 transcripts from both libraries were sequenced, generating 906 high quality sequences, 472 from the uninfected and 434 from the infected midgut library.