More and more evidence prove that deltamethrin (Del) exposure induced the adverse effect and damaged immune function to the aquatic animals in the parasite killing process with increasing insecticide application. However, little is currently known of the negative effect on mucosal immunity, especially in gills tissue. In this study, the LC50 of deltamethrin on gibel carp at 96h was determined to be 6.194 µg/L, and then juvenile gibel carp (Carassius auratus gibelio) (8.8 ± 1.0 g) were exposed to four Del exposure groups (0.61, 1.22, 2.44, and 4.88 µg/L) for 12h and 24h. To evaluate the innate immune-related enzymes in gills tissue, we measured the lysozyme (LYZ) and myeloperoxidase (MPO) contents and found that with increased concentration of Del exposure, the LYZ content was found to increase in the 1.22 µg/L Del group initially significantly and then gradually significantly decrease in the 4.88 µg/L Del group. And the activity of MPO was significantly lifted in a dose-dependent manner. The histological analysis showed that Del exposure serious desquamation and necrosis in the surface of epithelial cells are often found, accompanied by interlamellar cellular mass degenerative. In addition, the mucous cells were significantly decreased in the high Del concentration group (2.44 µg/L and 4.88 µg/L Del group) by AB-PAS staining. Importantly, totally 2857 DEGs (including 1624 up-regulated and 1233 down-regulated genes) were identified in the gill between the control group and 4.88µg/L Del exposure group using comparative transcriptional analysis. Among these, some genes involved in innate immune molecules, complement activation, apoptosis-related molecules, cytokine, and adaptive immune molecules, were also down-regulated. Importantly, we found several signal pathways related to immune response were downregulated, such as immune system process and tumor necrosis factor receptor (superfamily) binding pathways based on the GO and KEGG enrichment analysis. Consistently, we detect the expression of pro-inflammatory cytokines (TNF-a, IFN-?, IL-1ß, and IL-8), anti-inflammatory cytokines (TGF-ß), LYZ, IgM, and Hsp70 in the gills tissue at 12h and 24h after Del exposure, which were consistent with our sequencing results. Collectively, these results demonstrated that the gills mucosa injury and immunotoxicity was induced by Del exposure and provided novel insight for explaining to some extent why Del-exposure fish and are more susceptible to concurrent or secondary viral or bacterial infections. Overall design: Histopathology and transcriptome analysis of juvenile gibel carp (Carassius auratus gibelio) (8.8 ± 1.0 g) exposed to four Del exposure groups (0.61, 1.22, 2.44, and 4.88 µg/L) for 24h