In this study, the histopathological and ultrastructural alterations in the brain tissue of Oreochromis niloticus (Linnaeus, 1758) exposed to a sublethal concentration of diazinon standard for 21 days were determined. For this purpose, O. niloticus individuals were exposed to 280 µg/L (LC50/10) diazinon concentration for 21 days and on the 7th, 14th and 21st days of the exposure, the brain samples of these individuals were removed. After the histological and ultrastructural preparations of the brain samples, the prepared samples were evaluated with light and transmission electron microscopes (TEM). Examination of the samples indicated that a sublethal dose of diazinon induced histopathological and ultrastructural modifications in the brain tissue of O. niloticus. The severity of these alterations was increased with the duration of the time. The most severe histopathological alteration was necrosis determined on the 14th and 21st days of exposure. However, histopathologically the most frequent changes were cloudy swelling, hypertrophy and pycnotic nucleus in the glial cells of the brain. Ultrastructurally, mitochondrial degeneration, cristolysis, axon and dendrite deformations were seen in the tissues. These ultrastructural findings showed that the sublethal concentration of diazinon disturbed the energy metabolism of the cells which might result in neurodegenerative dysfunction of O. niloticus brain.