Abstract: Groups of zebra fish were injected with either PBS as controlor synthetic CpG-ODN 2006 for treatment, and 48 hours later, challenged by Vibrio vulnificus FJ03-X2 infection in this study. The immune protection of the treatment group reached a rate of 70.0% in 24 hours.RNA was extracted from the intestinal and kidney tissues and then reverse transcribed into cDNA. The mRNAs of lysozyme, Myd88, tlrs and tnf in the guts of the treated fish were significantly downregulated, while those of il1b and il10, significantly upregulated, as detected by Real-time RT-PCR.The differences on gene expression in kidney were even more apparent as the expression of lysozyme significantly upregulated, and those of il1b, myd88, tnf, ifng1-2, il10 and il22 significantly downregulated. It appeared that the CpG-ODN 2006 injection afforded the zebra fish to vitalize its immune system through regulating the expressions of non-specific immunity-related genes in the kidney and intestinesto ward off the viral attack.