In this investigation, the isolate of Pseudomonas aeruginosa from cystic fibrosis was highly resistant to β-lactarns and β-lactamase inhibitors. The resistant determinants of clinical isolate to imipenem, ceftazidime, ceftriaxone and cefepime were conjugally non-transfer. The slow or non-enzymatically mediated breakdown of imipenem and other broad spectrum p-lactams suggest the resistance of P.aeruginosa isolate to these drugs might be attributed to either permeability or efflux. Impaired penetration of imipenem and other p-lactams through the membrane was detected by a diminished expression of outer membrane (OM) proteins of approximate weight of 46 and 39 Kdal, matched to Opr D and OprF, respectively. Efflux resistance mechanism for meropenem and p-lactams has been ruled out since the isolate failed to express outer membrane protein of about 50 Kdal, which is matched to Opr M protein channel. Thus, reduced permeability in the clinical isolate may be the main mechanism conferring resistance against p-lactarns including imipenem.