Zebrafish were exposed to 25 μg/mL rifampicin （RIF），10 μg/mL oxytetracycline （OTC），2 mg/L potassium permanganate （KMnO₄），and 0.1 mg/L chlorine dioxide （ClO₂） for 12 hours to study the potential risks of the widespread use of antibiotics and disinfectants in aquaculture on the skin microbiota and immune responses of fish.Real time fluorescence quantitative PCR （qPCR） and 16S rRNA high-throughput sequencing were used to detect the immune responses and changes in the skin microbiota in zebrafish.The results showed that the exposure to antibiotics and disinfectants significantly upregulated the expression of inflammation-related genes including interleukin-1β （IL-1β），interleukin-6 （IL-6），and tumor necrosis factor-α （TNF-α） in zebrafish skin compared to the control group （P<0.05）.The relative expression level of immunoglobulin IgM，complement C3，and mucin Muc2 gene was significantly upregulated （P<0.05） as well.The Alpha-diversity indices including Chao1，Shannon，Ace，and Sobs of skin microbiota significantly decreased （P<0.05）.The results of principal coordinates analysis （PCoA） and non-metric multidimensional scaling （NMDS） showed that there was a significant separation in microbial clustering between the control group and the exposure group.Compared to the control group，the relative abundance of Proteobacteria increased in all exposed groups，while the relative abundance of Bacteroidota and Firmicutes decreased.The relative abundance of Acinetobacter increased in each exposure group，especially in the KMnO₄ treated group where the relative abundance reached as high as 65.36%.It is indicated that the exposure to antibiotics and disinfectants can induce inflammatory reactions and dysbiosis in zebrafish skin，weakening the function of immune barrier in skin and ultimately damaging the health of fish.