Background: E. coli belonging to the phylogenetic group B2 are linked to Inflammatory Bowel Disease (IBD). Studies have shown that antimicrobials have some effect in the treatment of IBD, and it has been demonstrated that E. coli Nissle has prophylactic abilities comparable to 5-aminosalicylic acid (5-ASA) therapy in ulcerative colitis. The objective of this study was to test if ciprofloxacin and/or E. coli Nissle could eradicate IBD associated E. coli in the streptomycin-treated mouse intestine. Results: After successful colonization with the IBD associated E. coli strains in mice the introduction of E. coli Nissle did not result in eradication of either IBD associated strains or an E. coli from a healthy control, instead, co-colonization at high levels were obtained. Treatment of mice, precolonized with IBD associated E. coli, with ciprofloxacin for three days alone apparently resulted in effective eradication of tested E. coli. However, treatment of precolonized mice with a combination of ciprofloxacin for 3 days followed by E. coli Nissle surprisingly allowed one IBD associated E. coli to re-colonize the mouse intestine, but at a level 3 logs under E. coli Nissle. A prolonged treatment with ciprofloxacin for 7 days did not change this outcome. Conclusions: In the mouse model E. coli Nissle can not be used alone to eradicate IBD associated E. coli; rather, 3 days of ciprofloxacin are apparently efficient in eradicating these strains, but surprisingly, after ciprofloxacin treatment (3 or 7 days), the introduction of E. coli Nissle may support re-colonization with IBD associated E. coli.