This research work was conducted in Uppanar estuary to ascertain the role of plasmids in the antibiotic resistance of bacteria. Water and sediment samples were collected for a period of three months. When tested against 20 antibiotics 22 MAR strains were isolated from the samples, which were found resistant to 5-13 antibiotics. They belong to 7 genera and 10 species. Gram-negative bacteria namely Neisseria mucosa, N. sicca, Branhamella catarrhalis, Klebsiella ozaenae, Citrobacterintermedius, Pseudomonas fluorescens and Enterobacter aerogenes were isolated. Gram-positive bacteria were of Bacillus subtilis, B. megaterium and Micrococcus luteus. When plasmid curing was done using acredine orange, the resistance against penicillin-G, ampicillin, tetracycline, amoxycillin, kanamycin, and chloramphenicol were totally lost in all strains, which confirmed the role of plasmid in these strains against antibiotics. Ten strains belong to different species were selected for the plasmid isolation and electrophoresis was done. Presence of plasmids in all strains was confirmed and the molecular weight was in the range of 2850 to 3170 bp. The study revealed that MAR strains are common in Uppanar estuary and they are plasmid mediated. This environment is seemed to be deteriorating at an alarming rate.