The current experiment was carried out to measure the effects of different concentrations of Fipronil on the immune response and health of Oreochromis niloticus through the evaluation of some immunological, biochemical and hematological parameters in addition to histopathological examination. Two hundred and forty Oreochromis niloticus were randomly distributed into four groups in triplicates. The first group served as a control. The second group exposed to 0.014 mg/which equal to1/3 96 hours lethal concentration (96 hrs LC50) for 4 days. The third and fourth groups were exposed to 0.0042and 0.002 mg/l (1/10 and 1/20 96hrs LC50) respectively for 10 weeks. The mortality rate in fish exposed to 0.014 mg/l of fipronil was 53%, meanwhile it was 21% and 8 % in fish exposed to 0.0042 and 0.002 mg/l for 10 weeks respectively. Fish exposed to fipronil showed pale gills and nervous manifestations beside congestion and hemorrhages of different internal organs. There was a significant decrease in the level of Immunoglobulin M (IgM) and lysozyme with concurrent increasing in the serum nitric oxide level compared with the control group. Significant increase in serum level of AST, ALT and Cortisol in all the exposed groups to Fipronil compared to the control group. Liver and gills of fish exposed to Fipronil showed different histopathological alterations.