Abstract: The aim of the research was to find out the effective antibiotic(s) against Escherichia coli and to observe the relationship between the plasmids to the antibiotic resistant pattern found by antibiotic sensitivity tests. For these forty water samples were collected from different sources including river, pond, tap and drain for isolation and identification of pure E. coli. The overall recovery rate of E. coli from water samples was 45%. The highest recovery rate was found from drain water (70%). The pure cultures were subjected to observe the antibiotic resistant pattern by commonly used ten antibiotic disks. All the isolates were found resistant to Penicillin G (94.45%) but 50% isolates were resistant to Amoxicillin. The isolates were highly sensitive to other antibiotics as Ciprofloxacin (88.89%), Chloramphenicol (72.22%), Norfloxacillin (88.33%) and Tetracycline (61.11%). The isolates exhibited moderate sensitivity to Ampicillin (44.44%), Gentamicin (77.78%), Streptomycin (33.33%). Only 22.22, 27.78, 27.78, 16.67, 11.11 and 16.67% of the isolates were recorded to show moderate sensitivity to Amoxycillin, Tetracycline, Chloramphenicol, Cephradin, Ciprofloxacin and Norfloxacillin, respectively. Plasmid profile analysis of 18 isolates were done by 0.8% agarose gel electrophoresis. A total of 11 different plasmid bands of different size were observed by careful eye estimation with the comparison to reference marker. The size of the bands range from 2.4 to 40 kb and at best 5 plasmid bands were found. There was no plasmid in only one isolate. There was no relation found between the plasmid band pattern in agarose gel and antibiotic resistance of E. coli.