Aspergilloses in humans are caused by several Aspergillus species, including Aspergillus flavus. Although the immune system of Drosophila is extensively studied, little is known about the fly's specific responses to A. flavus infection. Different strains of A. flavus vary in virulence in the fruit fly Drosophila melanogaster. We compared gene expression levels during induced infections in D. melanogaster between a highly virulent A. flavus isolate and a less virulent isolate, as well as from uninfected flies as a control. We found that 1081 of the 14,554 gene regions detected were significantly differentially expressed among treatments. Some of these up- and down- regulated genes were previously shown to be involved in defense responses against different pathogens. Some are known to be involved in vitelline membrane formation in flies. Genes expressed during the progress of the infection in flies may be related to those expressed in human aspergillosis, with potential to improve our knowledge of human innate immunity.