Serratia marcescens is an opportunistic bacterium that infects a wide range of hosts including humans. It is a potent pathogen in a septic injury model of Drosophila melanogaster as five bacteria directly injected in the body cavity of the fly kill the host within a day. In contrast, flies do not succumb to ingested bacteria for days even though some bacteria traverse the intestinal barrier into the hemolymph within a couple of hours. The mechanisms by which S. marcescens attacks enterocytes and damages the intestinal epithelium remain uncharacterized. To better understand intestinal infections, we performed a genetic screen for loss of virulence of ingested S. marcescens in which we identified FliR, a structural component of the flagellum, as a virulence factor. Next, we compared the virulence of two flagellum mutants fliR and flhD using two Serratia strains. Both genes are required for S. marcescens to escape the gut lumen into the hemocoel indicating that the flagellum plays an important role for the passage of bacteria through the intestinal barrier. In contrast, fliR but not flhD is needed to severely damage the intestinal epithelium and ultimately kill the host. Our results therefore suggest a flagellum-independent role for fliR in bacterial virulence.