Pathogenic bacteria are constantly adapted against antimicrobial drugs by arising new traits of drug resistance. The genes of such resistance are mostly possessed by pathogens due to the random use of antibiotics and commonly held on plasmid DNA. Plasmid-mediated antimicrobial resistance genes are easily transferred horizontally from one bacterial cell to another in an epidemic manner causing an increasing and serious challenge to clinicians to overcome the infectious pathogens. UTI is the most common infection caused by bacteria which has become hard to be treated due to the emerging problem of antibiotic resistance. The current study correlates plasmid DNA diversity and antibiotic resistance in E. coli; the common causative agent of UTI. Obtaining plasmid restriction maps provides a clear view about how DNA could be diversified in one bacteria. The result showed a clear DNA polymorphism in plasmids purified from E. coli. There has been 10 forms of different restriction plasmid profiles among 63 sample of E. coli. The 10 forms of plasmid profiles have been classified into two groups: highly diversified and lowly diversified profiles. Strains of highly diversified plasmid profiles showed significantly more resistance toward antibiotics than strains of less diversified plasmid profiles. Measuring plasmid DNA diversity together with the antibiotic resistance indicates an epidemic transfer and acquisition of different plasmids in pathogenic E. coli as a result of antibiotic random treatment.