The present study was focused for investigation the effects of sublethal concentration of nickel exposure after three weeks on some physiological and gill structure alterations in the freshwater fish, Oreochromis niloticus. Physiological parameters such as serum sodium, chloride, osmolality, glucose, cholesterol, total protein, albumin, amylase, lipase, alanine aminotransferase and aspartate aminotransferase were chosen to evaluate the response of experimental animal to nickel intoxication. In comparison with control, serum sodium, chloride and osmolality values were decreased in nickel-exposed fish, while the levels of serum glucose, cholesterol, total protein, albumin, amylase, lipase, alanine aminotransferase and aspartate aminotransferase were significantly elevated. Nickel exposure induced some histological changes in fish gill structure. These changes included hyperplasia, hypertrophy, shortening of secondary lamellae and fusion of adjacent lamellae. The physiological and histological changes indicate that nickel is very hazardous pollutant. Moreover, the above mentioned severe alterations indicate that the fish, Oreochromis niloticus is appropriate species to act as a biological indicator of water pollution level.