Abstract: In order to explore a green and economical breeding model for Ictalurus punctatus and provide guidance for fertilization management in its breeding process, we investigated the effect of fertilization on its gut microbiota. We designed a three-month experiment and divided the fish into three groups: organic fertilizer group (Y), inorganic fertilizer group (W) and control group (D). The intestinal contents of fish were collected and the intestinal microbiota was detected by 16S rRNA amplification technique. The results show that the diversity and abundance of intestinal microbiota decreased after fertilization. On phylum level, Firmicutes, Proteobacteria and Bacteroidetes were the dominant bacterial phyla. The relative abundance of Proteobacteria, Actinobacteria and Fusobacteriota in the control group was significantly higher than that in the fertilization group. On genus level, Romboutsia and Turicibacter were the dominant bacteria in the fertilization groups compared with the control group. The relative abundance of Streptococcus in the inorganic fertilizer group increased significantly (p<0.05). The relative abundance of Fusobacterium in the control group was higher than that in the inorganic fertilizer group (p<0.05). According to the difference analysis of the flora among the three groups, the content of lactic acid bacteria in the intestinal tract of fish in the inorganic fertilizer group increased significantly, while Streptococcus in the organic fertilizer group was significantly downregulated, reducing the incidence of catfish disease. The results show that the application of organic and inorganic fertilizer in aquaculture can promote the healthy growth of fish effectively.