One hundred ten samples from water and tilapia fish from 5 different location, River Nile Mansoura, Met-Annter drainage behind Talkha factory of fertilization, El-Tawilla drainage, Battra drainage and River Nile Damietta were collected for analysis of heavy metals, malathion in water and fish also analysis of water chemical parameters ammonia, nitrite, nitrate, chlorides, sulphates and total hardness, analysis hepatic glutathione system, some liver and kidney functions and blood picture The results showed highly significant increase of heavy metals and malathion in both fish and, water samples were collected from Met- Annter, El-Tawilla and Battra drainages. Malathion concentration in water was higher than in fish samples regarding to water chemical parameters ammonia, nitrite, nitrate, chlorides, sulphates and total hardness showed highly significant increase in drainages comparing with River Nile, and the presence of these chemicals parameters was higher in River Nile Damietta  than in River Nile Mansoura. Meanwhile the results showed shifting of the glutathione system manifested by dropping of total and reduced glutathione in hepatic tissue and increasing of oxidized glutathione in hepatic tissue. Moreover, showed significant increase in serum ALT, AST, creatinine and blood urea, while samples collected from River Nile in Mansoura were within normal level. Concerning to the red blood cell count (RBCs), heamoglobin (Hb) and packed cell volume (PCV) levels were lower than fish collected from River Nile at Mansoura which were in normal ranges. The total leukocytes count were in normal range in fish collected from River Nile Mansoura, in contaray total leukocytic count were increased in other polluted areas. Meanwhile shifting of glutathione system towards the oxidized side pointed to hepatotxic and nephrotoxic as these pollutants consider as an oxidant. The aim of this study was to know the water pollution and the reflection of this pollution on fish.  The study concluded that the heavy metals and other pollutants have a very dangerous effect on biochemical parameters and vital organs of fish.