Resistant strains of Escherichia coli were obtained against ciprofloxacin, ofloxacin, norfloxacin and HK-3140. Each resistant strain showed cross-resistance to other quinolones and peniciline-G. To find out the resistant mechanism, lipid and outer membrane proteins of the cells were separated and analyzed with gas chromatography and SDS denaturing gel electrophoresis. Lipid profiles from sensitive and resistant cells showed no big differences while outer membrane protein profiles showed a large variation. Sensitive cells showed better uptake of quinolone than resistant cells suggesting that the resistance against quinolone was resulted from the change in permeability through the outer membrane proteins.