The present study was carried out to compare between antibacterial activity of cefixime, norfloxacin and nitrofurantoin in-vitro and in-vivo after inducing urinary tract infection in rabbits by introducing pathogenic E.coli in the ureter by intra-rethral route, to reduce recurrent urinary tract infection caused by pathogenic E.coli. From the results obtained, it could be concluded that cefixime and norfloxacin at the therapeutic dose are more potent and efficient in comparison with nitrofurantoin in both in-vitro and in vivo study for reducing recurrent Urinary Tract Infection, the post antibiotic effect it was longer period in cefixime and norfloxacin showed long PAE.