An increase in salinity of the aquatic habitat can be an environmental stress factor for fresh aquatic organism, including fish. The present study investigated the impact of salinity and diet composition on digestibility and intestinal morphology of Nile tilapia. Triplicate groups of 35 fish weighing 35 g were fed a “Control” and “Test” diet and kept at salinity of 0‰ and 15‰ for 8 weeks. The diets were formulated using a different soybean meal content to create a contrast in alterations in intestinal morphology. Six fish per treatment were sampled for intestinal morphology analysis at the end of weeks 1, 4 and 8. The proximal, middle and distal intestine were processed for quantitative histology, in order to count the number of goblet cells and eosinophilic granulocytes; and to measure the thickness of lamina propria and sub-epithelia mucosa. The study showed that a salinity of 15‰ increased the nutrient digestibility; however this enhanced digestibility diminished over time. The intestinal morphology was influenced by both the salinity as well as the dietary soybean meal content. For soybean meal, the impact on morphology was largest in the proximal region of the intestine, whereas for salinity the largest impact was in the distal region. The negative effect of increased soybean meal on the lamina propria thickness was enhanced at a salinity of 15‰ and aggravated in time. Difference in nutrient digestibility induced by the salinity seemed not to be related to alterations in the intestinal morphology.