Lake Manzala is considered one of the most important costal Lakes in Egypt, where it is situated in the northern east part on the Mediterranean sea, receiving high load of different polluted waste water effluents, such as, Sewage water, industrial and agricultural wastes, from many drains, such as, Bahr El-Bakar , Ramsis, El-Sirw and Hadous drains, which affect badly the Lake environment to the eutrophic level, as well as human health among populations around the Lake.This study revealed the high pollution condition of water and fish samples which were taken from the most important sites (Kapoty, Bashtier and Mataryia areas), representative to the human activity and different ecosystems in the Lake water environment. Total suspended solids (T.S.S), Ammonia and nitrates, showed high figures exceeded the national and international legislations.Bacterial content was very high in this study, using plate count and different selective media, such as Plate count agar, end agar and Aeromonas differential agar. Total viable bacteria (T.V.B) reached more than 104 cfu/ml in water samples and 105 cfu/g in fish samples, particularly in Kapoty and Mataryia areas. Both faecal coliforms and Aeromonas spp counts reached 102 cfu/ml in water samples and 103 cfu/g in fish samples. Statistical analysis revealed very strong and strong positive correlation between Aeromonas spp counts and some minerals, such as Chlorides, Calcium and Magnesium, (r= 0.9, 0.8, 0.6 respectively- P > 0.001), which revealed the interaction and adaptability of such organisms with environmental factors.A total of 88 isolates from Aeromonas differential agar were identified using API 20E system, showed that 17% of these isolates belongs to Aeromnas hydrophila, and most of these strains were resistant to 3 or more antibiotics, such as Penicillin G, Ampecillin and Chloramphenicole.Isolaton of Plasmid DNA from these strains of Aeromonas hydrophila, showed that most of them harbouring Plasmids ranged from (Less than 2, 2 and 4 KbP).This could explain the adaptability and multi-drug resistance of such bacterial pathogenes, which could be involved in the infection course, and active causal agents of diahrroeal diseases in this important costal area of Egypt on the Mideterranean sea.