BACKGROUND: Intensive aquaculture, which is always associated with high concentrations of nitrogen pollu-tants, can lead to increased economic damage and energy loss, and increased fish mortality. OBJECTIVES: This study aimed to investigate the histomorphometry of the skin and stress indices of the Nile tilapia on exposure to different concentrations of ammonia. METHODS: In this study, Nile tilapia fingerlings were prepared and kept in the tub for adaptation, oxygenation, and feeding. A Range Finding test was performed on the fishes to find the ammonia killing range. Then, an acute toxicity test was performed on tilapia fish for 96 hours. For sub-lethal toxicity studies, 120 Nile tilapia fry were divided into 4 groups, including three groups based on different percentages of LC50 96 h (10, 20, and 30% LC50 96h) and a control group. The groups were exposed to ammonia for 14 days in an environment with constant tem-perature and pH control. Finally, histological examination and stress indices were performed on fish. RESULTS: The results showed that a higher concentration of ammonia resulted in tissue damage, including dis-coloration and skin blackening, and behavioral changes, including swallowing air from the water surface, decreased appetite and decreased mobility which finally resulted in death in these animals (P≤0.05). The highest and lowest glucose levels were reported for the control group and 2.7 mg/L. In addition, stress indices were significantly in-creased in experimental groups (P≤0.05). CONCLUSIONS: The data obtained from this study showed that increasing the amount of ammonia can lead to irreversible tissue damage to the structure of the skin and other tissues. In addition, the increase in oxidative stress in the Nile tilapia was due to the increase in ammonia, which led to lesions in these fish