Abstract: The experiment was designed to investigate the effects of sodium butyrate addition at different concentrations to the feed on growth performance, serum biochemical indices, intestinal antioxidant, and digestive enzymes in Pelteobagrus fulvidraco. A high-fishmeal diet (20% fishmeal and 0 cottonseed protein; positive control) and a low-fishmeal diet (10% fishmeal, 18.4% cottonseed protein; negative control) were formulated. Sodium butyrate was added to the low fishmeal diet group at 0.1% and 0.15%, respectively, resulting in four isonitrogenous and isofat experimental feeds by adjusting chicken meal, pork meal, maize protein meal, and soya bean meal. Pelteobagrus fulvidraco with an initial weight of 11 g was selected and randomly divided into four groups with three replicates (40 fish/replicate) and fed diets for a period of 56d. The results showed that compared with the high fishmeal group, the average final weight, weight gain rate, alkaline phosphatase (AKP), lipase (LPS), superoxide dismutase (SOD) activity, expression of the anti-inflammatory factor IL-10, and the length of intestinal villi, as well as the contents of Pseudomonas spp. and Methylobacillus spp. of Pelteobagrus fulvidraco in the low-fishmeal group were all significantly decreased (P<0.05), whereas serum ghrelin transaminase (GPT), ghrelintransaminase (GOT), and intestinal malondialdehyde (MDA) levels were significantly increased (P<0.05), the expression of intestinal pro-inflammatory factor TNF-α, pro-apoptotic genes P53, and Caspase-3 was significantly up-regulated (P<0.05), and the level of Pseudomonas spp. and Methylobacillus spp. in the intestines was significantly increased (P<0.05). After the addition of sodium butyrate to the feed with low fishmeal, the final mean weight as well as the weight gain rate showed a significant increase (P<0.05) compared to the low fishmeal group. The serum glutamate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) levels of Pelteobagrus fulvidraco in the group with 0.10% sodium butyrate were significantly decreased (P<0.05), whereas the serum levels of alkaline phosphatase (AKP), acid phosphatase (ACP), and urea nitrogen (BUN) levels were significantly increased (P<0.05), LPS, AMS, and SOD levels were significantly elevated (P<0.05) and MDA levels were significantly decreased (P<0.05) in the group supplemented with sodium butyrate, and peroxidase (CAT) content was significantly elevated (P<0.05) in the group supplemented with 0.15% sodium butyrate. The expression of TNF-α, P53, and Caspase-3 was down-regulated (P<0.05), the expression of IL-10 and Occludin was significantly up-regulated (P<0.05), the height of intestinal villi was significantly increased (P<0.05) in the group of added sodium butyrate, and the level of Pseudomonas spp. in the intestines was significantly reduced (P<0.05) in the group of 0.15% sodium butyrate. In conclusion, dietary sodium butyrate supplementation improve growth performance, enhance intestinal antioxidant capacity, alleviate intestinal inflammation, promote villi development, and suppress harmful flora microbiota in Pelteobagrus fulvidraco, thereby maintaining the homeostasis of the intestinal flora.