This study aimed to investigate the effect of substitution of extruded soybean meal (ESM) (Digesta™) on growth performance, carcass characteristics, immune responses, biochemical variables of blood, and nutrient digestibility of ileal in broiler chickens (Ross 308). 225 chicks were randomly distributed among 5 trial groups (3 replicates of 15 chickens). The dietary treatments included different levels (0, 25, 50, 75, and 100%) of diet replacing ration of soybean meal with ESM which were fed to birds during a 42-day experimental period. The results showed that chickens fed diets 75% or 100% ESM had the highest (P <0.001) daily overweight rates and also had the best FCR. The results showed that the treatments had a significant effect on carcass parts. Replacement of 50% of soybean meal with ESM resulted in the decreased ventricular area and increased percentage of chest compared to the control group (P <0.05). Replacement of 75% soybean meal with ESM increased the antibody titer against the influenza virus in comparison with other experimental groups (P <0.01). The serum triglycerides, glucose, and uric acid (UA) were decreased by the replacement of soybean meal with ESM (P <0.05), but the total protein showed an increase by the increasing ESM to 100 % (P <0.01). Substitution of 75% and 100% of ESM in diets decreased the activity of enzyme aspartate aminotransferase (P <0.01) and increased triiodothyronine hormone (T3) (P <0.05). The use of ESM in all substitution levels increased the carcass protein content (P <0.001) and improved ileal digestibility of crude fat (P <0.01). Also, the highest ileal digestibility coefficients of protein were observed in the chickens fed diets 75 % or 100% ESM. In conclusion, the results of this experiment indicate that the extruding process of SBM has a beneficial effect on growth performance and nutrient digestibility in broiler chicks.