Application of nanotechnology is increasingly expanding and discharge of nanomaterials into aquatic ecosystems is inevitable. The present study was carried out to evaluate the pathological effects of various concentrations of nickel oxide nanoparticles in the diet of (O. mykiss) along with the ability of this species to regenerate and recover its biological activities in the presence or absence of dietary silymarin. To that end, 1200 fish (3.83±0.01g) were randomly allotted into eight distinct treatments with 3 respective replicates. Treatments included control group without any supplemental nickel oxide nanoparticle or silymarin and other experimental groups comprising various levels of dietary nickel oxide nanoparticles (0, 100 and 500 mg/kg feed) and silymarin (0 and 1 g /kg feed). Gill tissues were taken at two stages (at the end of the first and second month of the experiment). Different pathological alterations including aneurysm, fusion of secondary lamella, congestion, epithelial cells hyperplasia and epithelial lifting observed in fish fed with diets containing nanoparticles. Results showed that treatments fed with diets containing both nickel oxide nanoparticles and silymarin had lower degrees of gill tissue pathological alterations in comparison to those fed with diets which only had nanoparticles. In conclusion, silymarin supplementation protected gill tissues against dietary nanoparticle contamination due to its antioxidative activities.