The basal diet(A) contains 25% fish meal as control, and four isonitrogenous isoenergic yeast extract experiment diets, which substituted 15%(B), 30%(C), 45%(D) and 60%(E) fish meal in basal diet, were fed to the Litopenaeus vannamei (7.50±0.13) g respectively for 42 d, then superoxide dismutase (SOD) activity and lysozyme (LSZ) activity in haemolymph and the expressions of lysozyme mRNA and Toll receptor mRNA in gill were detected. The shrimp were also challenged with Vibrio alginolyticus. The results showed that: LSZ activity in haemolymph in 15% group was significantly higher than that of control (P<0.05). There was no significant difference of SOD activity in haemolymph, the expressions of lysozyme mRNA and Toll Receptor mRNA in gill between alternative groups and control group (P>0.05). The cumulative mortality of 60% group at 24 h and 48 h was significant higher than that of control (P<0.05), and there was no significant difference of cumulative mortality between alternative groups and control group at 72 h and 96 h (P>0.05). It is therefore suggested that yeast extract can replace 45% fish meal of the diets without affecting immunity and vibrio resistant ability of the shrimp.