Crohn's disease (CD) is an inflammatory bowel disease (IBD) of unknown aetiology. Genetically engineered rodent models showed that IBDs are immunologically mediated and that luminal bacteria play an essential role in the development of the inflammation. Various bacterial pathogens have been incriminated but results have been conflicting. A new pathovar of E. coli, designated adherent-invasive Escherichia coli (AIEC) may be associated with CD. AIEC strains colonize the intestinal mucosa by adhering to intestinal epithelial cells. They are also true invasive pathogens, able to invade intestinal epithelial cells via a macropinocytosis-like process, and to survive and replicate intracellularly after lysis of the endocytic vacuole. Within macrophages, AIEC strains survive and replicate extensively without inducing host cell death and induce the release of high amounts of TNFalpha. All these virulence properties designate AIEC as a possible pathogen potentially able to induce persistent intestinal inflammation, by crossing and breaching the intestinal barrier, moving to deep tissues, and continuously activating macrophages.