A total of 60 Nile tilapia fish Oreochromis niloticus were collected from River Nile (Damietta branch): Weesh El-Hagar village during late summer. An experimental infection was applied on apparently healthy Nile tilapia (three equal groups) by intramuscular injection of 0.1 ml of 2.4X10⁷ CFU/ml of well identified A. hydrophila suspension isolated from freshwater crayfish P. clarkii, while, the third group was injected 0.1 ml of sterile buffered saline . The clinical picture, morbidity and mortality rates were recorded for 7 days. The results showed that all injected tilapia died by the end of experiment with a mortality peak on the 3^rd day, while the morbidity started to appear by the 2^nd day (10%). The histopathological alterations were recorded and discussed. This study suggests an epidemiological significance of Aeromonas hydrophila and the role of crayfish in its transmission.