The aim of the present experiment was to study the effects of quorum quenching enzyme AI-96 against Aeromonas hydrophila NJ-1 attack with the bath challenge in zebrafish. The experiments set two dietary groups for zebrafish,1) basal diet as control, 2) enzyme-containing diet with 3 U/g food of AI-96. Zebrafish tissues (gill, liver, kidney and intestine) were sampled at day 0.5, 1, 3, 7 and 14 after co-bath challenge with live Aeromonas hydrophila NJ-1 at two doses (high 2.5×10 8 cfu/mL, low 0.7×10 8 cfu/mL). The populations of NJ-1 colonizing in the tissues were quantified by real time PCR, and accumulated mortality of zebrafish were recorded everyday. Results showed that after challenge, the NJ-1 were detectable in the tissues of the attacked zebrafish in the total population order of intestine> gill > liver > kidney. More NJ-1 colonized in the tissues in the high dosage challenge treatment than the low group. Interestingly, the diets containing AI-96 enzmye significantly decreased the colonizing populations of NJ-1 in the zebrafish (P < 0.05), compared with the counterparts fed with basal diets when the fish was chanllenged with 2.5×108 cfu/mL NJ-1. In 0.7×10 8 cfu/mL challenge treatment, the NJ-1 number colonizing in gill (3d), intestine (0.5, 1, 3, 7, 14 d), liver (3 d) and kidney (7 d) were also lower in the fish treated with AI-96 containing diets than the ones with basal diets (P < 0.05). Moreover, these effect was more obviously in 0.7×10 8 cfu/mL challenge treatment after 7 d (P < 0.05). Therefore, the dietary AI-96 enzyme could improved the survival rate against NJ-1 attack in both challenge levels, For this reason, quorum quenching enzyme could effectively protect zebrafish against A. hydrophila at 0.7×10 8 cfu/mL level in zebrafish.