Hydrogen sulfide (H2S) is generally recognized as a highly poisonous environmental and industrial pollutant. Previous toxicological studies of H2S are mainly focused on the nervous and cardiovascular system. There are few reports on the H2S toxicity effects on jejunum to our knowledge. Our study examined the morphological changes and antioxidant functions of broiler jejunum after the 42-day exposure to H2S. Effects of H2S on morphological damage and immune function in the broiler jejunum were analyzed from the perspective of CYP450s and oxidative stress via transcriptomics and quantitative real-time PCR (qRT-PCR). It was found that the activities of GPx, CAT, SOD, and T-AOC and the level of GSH were observably decreased (P < 0.05), while the contents of MDA and H2O2 were remarkably increased (P < 0.05) in the jejunums of broilers exposed to H2S, which undergone a process of oxidative stress, and typical inflammatory changes and apoptosis could be observed. Transcriptional profiling results showed that 208 genes were significantly up-regulated while 295 genes were remarkably down regulated in H2S group. The expression of CYP450s, inflammation and apoptosis-related genes were also significantly increased. In conclusion, H2S led to the redox homeostasis disorder through CYP450s differential expression in broiler jejunum. The jejunal inflammatory response, apoptosis along with the immune dysfunction were subsequently observed, which eventually caused jejunal morphology and functional damage. The present study further enriches and perfects the mechanism theory of H2S toxicity on broilers, which may be valuable for the risk assessment of H2S and human health protection. (C) 2018 Elsevier Ltd. All rights reserved.