Ps. aeruginosa a well-known opportunistic bacterium infects various tissues and organs causing sever problems. In tropical and semitropical countries and because of environmental and sanitizations reasons Ps. aeruginosa acquiring more virulent factors, gained multi-resistant genes, adapt resistant mechanisms for antibiotics, drugs, disinfectants and in general for any toxic compound. Six multidrugs resistant strains out of 260 different bacteria isolated from patients at Tanta University hospital, Tanta, Egypt, used in this study. To evaluate the role of divalent cations in antibiotic resistance we used a medium containing Ca(2+) and Mg(2+). Various antibiotics tested with or without the LC(10) and LC(50) equivalent amount of EDTA against each strain. We found that after adding EDTA, 70% of the strains turned from resistant to sensitive, especially considering those antibiotics, which inhibit protein synthesis, such, as tetracycline. Simple experiment for testing the effect of Antibiotic-EDTA combination on Rabbits skin artificial ulcer(s) infected by Ps. aeruginosa significantly improve the efficiency of using such combination in superficial treatment. We propose using media other than Muller-Hinton agar in antibiotic sensitivity test to select the best antibiotics could be used in vivo or in superficial treatment. A combination between a proper amount of EDTA and antibiotics especially protein inhibitors will improve the control of Ps. aeruginosa.