The histopathological changes and behavioral changes of the fish challenged with four different salinity treatments including a control (0, 5, 20 and 35 ppt) for 96 hours was studied. The Tilapia fingerlings with the size 10-14 cm total length acclimated successfully to freshwater before introduced to hyper-saline environment. The results showed that all fish survive in 0 ppt and 5 ppt, while 75% death in 20 ppt and 100% death in 35 ppt. The mortality rate was increased with increased of salinity. Fish exposed to different salinities exhibited clinical signs agitated behavior, respiratory distress, abnormal nervous behavior and death were recorded. Degeneration, necrosis, hemorrhage and hyperplasia of kidney and gills were observed as major histopathological changes.