Background: Pseudomonas aeruginosa is considered as one of the top five pathogens of nosocomial diseases worldwide. Infections caused by P. aeruginosa are often severe and life threatening and are difficult to treat because of the limited susceptibility to antimicrobial agents and the high frequency of emergence of antibiotic resistance during therapy. What adds to the problem of P. aeruginosa nosocomial infections is the emergence of multi-drug resistant (MDR) strains that develop resistance by various mechanisms like multi drug resistance efflux pumps, production of β-lactamases, aminoglycoside modifying enzymes and decrease outer membrane permeability. Efflux pumps contribute to multidrug resistance as they expel different types of antibiotics and chemicals. Objectives: Detection of the role of the efflux pump in multidrug resistant P. aeurginosa isolates from Suez Canal university hospital (SCUH) in Ismailia. Methodology: This study included 307 hospitalized patients of both sexes and from all age groups. A forty nine P. aeruginosa strains were isolated from blood, urine, sputum and pus. Antibiotic susceptibility tests were done by using disc diffusion method. For detection of the role of efflux pump in MDR, strains proved to be MDR were further tested by MIC (agar dilution susceptibility method) before and after addition of efflux pump inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Results: The isolation rate of P. aeruginosa was 15.9% out of a total number of 307cases. The isolation rate was highest from cases in the ICU (26.5%), while it was lowest from internal medicine department (8.2%). 57.1% of the isolates were multidrug resistant; the efflux pump mediated resistance was proved for ciprofloxacin and meropenem. Conclusion: Our study proved the role of efflux pump mechanism in mullti-drug resistance by P.aeruginosa isolates to ciprofloxacin and meropenem. Other studies proved the role of this mechanism in resistance to carbapenem, levofloxacin, ciprofloxacina and meropenem. Understanding the mechanisms by which these pumps act and how to overcome its activity opens the door for restoring the antibiotic activity and constitute a promising target for novel antibacterial agents.