The emergence of new pathogenic bacteria resistant to most, if not all, currently existing antimicrobial agents has become a serious problem in modern medicine, particularly because of the affiliated increase in immunosuppressed inhabitants worldwide. The recent surfacing of E. coli O157:H7 as a foremost food pathogen is a lively reminder of its dynamic character. Mounting concerns about drug-resistant pathogenic bacteria have rekindled interest in alternative treatments of bacterial infections. Prominent among these alternatives is phage therapy for combating supportive infections. This observation particularly calls for the in vivo examination of environmental phage candidates to treat stx1A and stx2A positive Escherichia coli O157:H7 induced experimental diarrhea. Two O157-specific lytic bacteriophages PAH6 and P2BH2 were isolated from sewage and characterized. Healthy conventional Swiss albino mice were used for investigating the O157:H7 specific diarrhea applied through three alternative routes (oral, intramuscular and intraperitoneal).The highest titer of orally added E. coli 0157:H7 was found to be fatal within 24 hrs. A single oral dose of phage strain (1X107 PFUml-1) alone or in combination was sufficient to rescue 100% of the animals from this lethal challenge in vivo. Finally, the results obtained in this study suggest that cocktail of two coliphages applied orally for treatment gastrointestinal infection have good therapeutic potential.