Animal protein is an indispensable source in the feed of carnivorous fish. Fish meal, as a high-quality animal protein, has high price and limited source due to the adverse impact of resources, storage and recent international situation. Because of its rich nutritional value, high digestibility, balanced amino acids and high biological conversion rate, poultry by-product meal has attracted much attention from the animal protein source production market. Therefore, the application effect of poultry by-product meal in the feed of Micropterus salmoides was systematically evaluated in order to understand the quality and safety of domestic poultry by-product meal, and to provide a theoretical basis for rational use of meat meal. To evaluate the feasibility of replacing fish meal with poultry by-product meal, five isonitrogen-isolipid experimental diets (control, PBM 12.5, PBM 25.0, PBM 37.5, PBM 50.0) were formulated. M. salmoides [initial body weight (9.25±0.13) g] was fed the system for 8 weeks. The results showed that there was no significant difference in the weight gain rate(WGR) , specific growth rate (SGR) and feeding ratio(FR) of each group during the breeding period of M. salmoides. Compared with the control group, the activities of total superoxide dismutase (T-SOD) and catalase (CAT) of all experimental groups in liver were significantly increased, while the content of malondialdehyde (MDA) was significantly decreased. With the increase of replacement level, the relative expression levels of anti-inflammatory cytokines (IL-10, TGF-β) in liver were significantly up-regulated, while the relative expression levels of pro-inflammatory cytokines (IL-8, TNF-α) were significantly down-regulated, but had no significant effect on the clinical symptoms of liver tissue structure. In addition, with the increase of replacement level, the relative expression levels of intestinal antioxidant genes (sod and cat) and intestinal tight junction protein genes (Occludin, ZO-1 and Claudin-1) were significantly up-regulated, while the contents of D-lactate (D-lac) and lipopolaccharide (LPS) in serum were significantly decreased. In conclusion, replacing 50% fish meal with poultry by-product meal in the basal diet (40% fish meal) did not inhibit the growth of largemouth bass, but also it can enhance the antioxidant capacity and immunity of fish, and improve the liver and intestinal health of M. salmoides. Therefore, poultry by-product meal can be used as a high quality protein source for M. salmoides feed.