Pesticides especially insecticides are widely used in the field of agricultural development all over the world to increase crop production. Moreover, exposure to such compounds does not only influence the intended targets but also induces adverse impacts on a number of unintended targets in animals. This research aimed to determine the toxic impacts of lufenuron (an insecticide) on the health status of fish in terms of measurement of oxidative stress, antioxidant enzymes, DNA damage and histopathological changes in Nile tilapia (Oreochromis niloticus) exposed to different concentrations. For this purpose, Oreochromis niloticus fish, weighing about 75-80g were arbitrarily separated into four different groups and then exposed to lufenuron @ 0.7, 1.2 and 1.7µg/ L for 39 days. The results showed that the fish exposed to the pesticide had significant changes in oxidative stress, antioxidant profile in gills and percentile rate of DNA damage in different visceral organs including liver, kidney, and gills. Results of light microscopic investigations indicated different histological changes in liver (necrosis of hepatocytes, degeneration of hepatocytes, vacuolar degeneration and congestion), gills (necrosis of lamellar epithelial cells, telangiectasia, and atrophy of secondary lamellae), heart (congestion, necrosis of neurons, microgliosis and intracellular edema), brain (congestion, myofibrosis, neutrophilic and myocarditis) and kidneys (necrosis of renal tubules, widening of urinary space, necrosis of renal tubular epithelial cells). A significantly escalate in oxidative stress while lower quantity of antioxidant biomarkers was documented in experimental fish. The findings of this study suggest that long-term exposure to lufenuron has negative health effects via induction of DNA damage, increased oxidative stress, lowering of enzymatic antioxidants profile and histological lesions in visceral organs of Nile tilapita (Oreochromis niloticus).