Untreated or poorly treated industrial wastes, heavy metals and other pollutants are released into the Nile Delta canals network; causes accumulation of various heavy metals in the fish from sediments, water and food. The present study aimed to evaluate the effect of heavy metals on the ovary of Tilapia zillii in some River Nile canals, at Nile Delta, Egypt. A total of 502 specimens of adult Tilapia zillii were monthly collected from Zifta, Shubra Malakan and El-Nasria stations at El-Gharbia Governorate, during the period from December, 2017 to November, 2018. Heavy metals (Cu, Pb, Ni, and Cd) were measured in the ovary of the fish at three stations. Histopathological changes in the ovary were photographed and described. Results showed that the highest annual averages value of heavy metals concentrations in the ovary of T. zillii were recorded at El-Nasria station, followed by Shubra Malakan station and reached to its lowest value at Zifta station. The mature oocytes in the ovaries of Tilapia zillii had the highest value (74.43%) at Zifta, medium value (49.87%) in the ovaries fish at Shubra Malakan and lowest value (15.07%) in the ovaries of fish at El-Nasria. The percentage of mature oocytes decreases and atresia increases with increase heavy metals concentrations. Therefore, stopping of maturation was noticed in some ovaries of fish collected from El-Nasria station (with the highest heavy metals concentrations). The histopathological features in the ovaries of T. zillii, collected from Shubra Malakan and El-Nasria stations showed degenerative and necrotic changes in the oocytes and proliferative changes in most oocyte's granulosa. The ovarian cells of T. zillii converted to testicular cells. The histopathological alterations observed in the ovary may be attributed to the effects of heavy metals in the agricultural, industrial and sewage wastes discharged into El-Nasria station at Omar Bey Drainage. This study concluded that the increase in heavy metals causes increased atresia in the ovary Tilapia zillii. Therefore, the technical treatment must be made to the agricultural, industrial and sewage wastes discharged into Omar Bey Drainage.