In order to compare the effect of substituting fish meal with fermented soybean meal and soybean meal, and confirmed whether the benefit from the two feed materials was related to the content of inclusive soybean antigen protein, two experiments were designed. In experiment 1, one of the two practical diets contained 24.9% soybean meal (SBM), the other one containing 8% fermented soybean meal and 16.95% soybean meal (FSBM); in experiment 2, two semi-purified diets were included with high antigen protein (SPD1) and low antigen protein (SPD2) approximately equal to SBM and FSBM group respectively in experiment 1. Diets were fed to Litopenaeus vannamei (initial weight: 7.48 ± 0.24 g) for 60 days. The results showed that in experiment 1, growth performance was not significantly different between two groups, the enzyme activity (AKP, AST, ALT, SOD and LZM) and mRNA expression levels of TLR, LZM, IMD and HSP70 were significantly higher in the SBM group; In experiment 2, weight gain and specific growth rate were significantly higher in the SPD2 group, while higher activities of AKP, ALT and LZM, lower expression levels of TLRmRNA, LZMmRNA and IMDmRNA and higher expression level of HSP70mRNA were found in SPD1 group. These results implied SBM was more likely to induce stress reaction in shrimp than FSBM, which were closely related to the antigen protein in SBM.