The aquatic environment is particularly suffered from the various contaminants due to industry, urbanization and agriculture activities. The present study was carried out to study histological structural of liver in the freshwater fish, Oreochromisniloticus, which collected from different localities and exposed to different pollutants. Histological, histochemical, and Immunohistochemical alterations were examined in liver .Samples from El-Riah El-Menoufy and downstream of El-Rahawy area, indicated that, the Last one is more suffered from many histopathological changes than those collected from El-Qanater El-Khyria.As well as, a decrease in carbohydrates distribution, an elevation of different types of fiber and a strong caspase-3 expression are detected. The histopathological damages were related to the discharge of water loaded with sewage in El-Riah El-Menoufy and El-Rahawy drain, which consequently may affect fish and human health. The present study also investigated the concentrations of some heavy metals in river water (iron, copper, zinc and cadmium) and their effects on Nile Tilapia obtained from the same investigate sites. Accordingly, there is a necessity to treat the sewage effluents before discharging to the Rosetta branch.