Origanum vulgare essential oil (OEO) was added in diets of Basa fish (Pangasius hypophthalmus) at levels of  0.0, 5.0, 10.0, 15.0, and 20.0 g /kg feed to determine its effects on antioxidative capacity, immunity, histopathology, expression of immune-related genes and resistance to Aeromonas hydrophila. After 2 months of  feeding experiment, serum lysozyme, superoxide dismutase and catalase enzymes have been dramatically increased according to the levels of added (OEO) , the highest level was at group fed on 20 gm /kg feed and 15gm/kg feed while, the lowest level at the control group also the expression of interleukin-1beta and toll-like receptor 2 genes in kidney tissues have been increased as the same manner .OEO-supplemented diet pereserves the normal architecture of liver, gills, intestines, and kidneys in all experimental groups. The scores of the histopathological lesions were significantly decreased with presence of regeneration to damaged cells  in groups fed 20 gm OEO/kg feed &15 gm OEO/kg feed. After pathogenic A. hydrophila challenge the mortality percent after 10 days of the challenge experiment promptly reduced and the percent of survival of Basa fish was relatively increased by OEO administration according to the given dose . Findings show that the OEO in diet has improved the antioxidative status, immunological responses, histopathology, evaluation of immune related genes expression of Basa fish against A. hydrophila infection.