Background: The resistance of E. coli isolates to fluoroquinolone is a significant challenge to antibiotic treatment and infection control policies. A significant increase of ciprofloxacin-resistant E. coli has occurred during last years, indicating the need for further analysis. Objective: The current study was aimed to detect quinolone-resistance in multi-drug resistant E. coli isolates that were recovered from patients with urinary tract infection in the Urology and Nephrology center of El-Mansoura University, Egypt. Methods: The clinical uropathogenic specimens collected were studied. Identification and antimicrobial susceptibility testing were done using VITEK 2. Minimum inhibitory concentrations (MICs) of different quinolones were determined for fluroquinolone resistance (FQ-resistant) isolates. Also, they were screened for the presence of the plasmid mediated quinolone resistance (PMQR) qnrA, qnrB and qnrS genes by polymerase chain reaction (PCR) techniques. Results: In the present study, 100 (32.7%) E. coli of 305 uropathogenic specimens were tested. The patients involved in this study included both genders, females (76%) were the most affected group of patients as compared to males (24%). The quinolones resistance rate was 30% of the isolated E. coli samples. The detected genes for the quinolone's resistance samples were: 14 (46.6%) qnrB, 13 (43.3%) qnrS and 2 (6.6%) qnrA. Conclusion: This study identified quinolone resistance (qnr) gene in uropathogenic E. coli in EGYPT. These finding which suggest a possible resistance to quinolone are of high interest for better management of patients and control of antimicrobial resistance in Egypt.