Tributyrin (TB) has applications as a growth and intestinal health promoter for animals. A 10-week feeding trial was conducted to evaluate the application of TB to relieve the negative effects induced by high cottonseed and rapeseed meal (CRM) in juvenile grass carp (Ctenopharyngodon idellus; initial weight 9.59 ± 0.01 g). Grass carp were fed a normal fish meal (FM) diet (positive control [PC], 50 g/kg FM, 340 g/ kg CRM), high CRM diet (T0, 20 g/kg FM, 540 g/kg CRM) or a T0 diet supplemented with 500 (T500), 1000 (T1000) and 1500 (T1500) mg/kg TB. The results showed that (1) grass carp fed diet T0 displayed the poorest growth (p < .05), whilst no significant differences in growth performance were observed in those fed diets PC and T1000.(2) Complement 3, glutathione peroxidase and superoxide dismutase levels in the T0 group were significantly lower (p < .05) than those in the PC group. The immune indices of fish fed the 1000 or 1500 mg/kg TB diet were significantly higher (p < .05) than those of fish fed the T0 diet, whilst there was no significant difference with PC group. (3) Compared with that of the T0 group, pro-inflammatory cytokine (il-6, il-8, nfκb and tlr-4) expression in the 1000 mg/kg tributyrate group was significantly downregulated, whilst the expression of anti-inflammatory cytokines (il-10 and thfβ) and intestinal tight junction proteins (zo-1, zo-2, claudin-b, claudin-c and occludin) was significantly upregulated (p < .05). In conclusion, high CRM diets induced negative effects on grass carp, and dietary TB supplementation promoted growth, improved antioxidant capacity and enhanced intestinal barrier function of grass carps. And the optimum supplemental level of TB was 1000 mg/kg.