This study was carried out to assess the insulin-like growth factor-1 (IGF-1), levels of some physicochemical parameters and heavy metals in water collected from the River Nile. The results showed that the physicochemical concentrations of the water samples were as follows: temperature 16.3-36.5°C, transparency 54.3-80.2 cm, electrical conductivity 268-320 μS/cm, pH 7.5-8.3, dissolved oxygen 7.3-11.2 mg/l, biochemical oxygen demand 1.3-3.3 mg/l, chemical oxygen demand 6.3-10.7 mg/l, and ionized ammonia 0.57-0.96 mg/l. Heavy metals (Fe, Mn, Cu, Zn, and Pb) in water showed maximum values as follows: (5.8, 0.51, 0.350, 0.230 and 0.90 mg/l) and (5.2, 0.42, 0.13, 0.47, and 0.27 mg/l) in summer and winter, respectively. The levels of metals detected in the tilapia muscle were higher than those found in water. Increased activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was detected in the blood analysis of O. niloticus. Levels of urea, uric acid, glucose, cholesterol and insulin-like growth factor-1 (IGF-1) were high in fish collected from polluted sites (iron and steel factory at Helwan, sugar cane factory at El-Hawamdia, Road El-Farag, and Electricity station at Shobra El-khima). In addition, a significant increase (P<0.05) was shown in the activities of catalase (CAT), superoxide dismutase (SOD), and level of malondialdehyde (MDA) when compared to reference station (V) EL-Qanater. The results indicate that Nile tilapia resisted oxidative stress induced by heavy metal exposure by antioxidant mechanisms.