Abstract: To evaluate effects of the oxidized fish oil on the antioxidative stress pathways of intestine, grass carp Ctenopharyngodon idellus were fed oxidized fish oil and normal fish oil for 7d before collecting intestinal mucosa for histology and RNA-seq. The gene differential expression, the gene annotation and IPA gene pathway were analyzed. Severe damage was observed in the intestine of grass carp by oxidized fish oil. The RAN-seq results indicated increased Keap1-Nrf2-ARE signal pathway and GSH/GSTs pathway by oxidized fish oil treatment. The heat shock proteins and ubiquitin - proteasome system genes were also significantly up-regulated. The activations of these three anti-oxidation pathway systems serve the main components to remove the damaged cells and decompose the harmful proteins, which play the essential roles to protect the intestinal mucosa tissue and its cells and to repair the intestinal mucosa response to the oxidation injury.