Chloroquine has been described to increase Plasmodium infectivity to the mosquito vector and is known to affect the vertebrate host immune response including during malarial infection. Although knowledge of the mosquito immune response has recently improved, nothing is known about the impact of chloroquine on mosquito immunity. In order to characterize the influence of chloroquine on the mosquito immune system, we have analyzed the effect of chloroquine on Anopheles gambiae (i) serine proteases and (ii) antimicrobial peptide gene expression, in uninfected and Plasmodium berghei infected mosquitoes, using real-time PCR. We have demonstrated for the first time that mosquitoes fed on chloroquine-treated mice showed a significant down regulation of some immune-related genes. This effect was independent of midgut bacterial burden. These results suggest that chloroquine might act on the Anopheles serine proteases cascade, interfering with signal transduction pathways and at a transcriptional activation level.