The aim of the present study was to investigate the effects of dietary sodium butyrateon growth performance, intestinal microbiota, digestive enzymes, humoral immune responses and resistance against Aeromonas hydrophila in rainbow trout (Oncorhynchus mykiss) juveniles (39.5±1.12 g). The fish were fed diets supplemented with 0 (SB0), 1.5 (SB1.5), 2.5 (SB2.5) and 5 (SB5.0) g/kg sodium butyratefor 45 days and challenged with A. hydrophila thereafter. The results showed that 2.5 and 5 g/kg sodium butyratesignificantly increased growth rate and feed efficiency, compared to the SB0 group. Red blood cell (SB2.5, SB5.0), white blood cell (SB1.5, SB2.5, SB5.0), hematocrit (SB2.5) and hemoglobin (SB2.5), plasma total protein (SB2.5), lysozyme (SB2.5), bactericidal activities (SB1.5, SB2.5, SB5.0), intestinal total bacteria (SB1.5, SB2.5, SB5.0), lactic acid bacteria (SB2.5, SB5.0), stomach pepsin activity (SB2.5), intestinal trypsin (SB1.5, SB2.5, SB5.0), chymotrypsin (SB2.5), protease (SB1.5, SB2.5, SB5.0), and amylase (SB2.5, SB5.0) activities significantly increased by dietary sodium butyrate inclusion. Post-challenge survival showed no significant difference among the treatments; however, mortality was numerically in the following order: SB5.0 (64.4±7.07%), SB2.5 (57.8±2.67%), (SB1.5 51.1±7.07%) and SB0 (44.4±7.07%). In conclusion, dietary sodium butyrateat 2.5-5 g/kg is recommended as a feed supplement for rainbow trout to augment the fish growth and disease resistance. Such beneficial effects of dietary sodium butyratein rainbow trout might be due to the changes in intestinal microbial communities, which in turn improve nutrient availability and immune function.