The grass carp, Ctenopharyngodon idella (Valenciennes), is one of the most extensively aquacultured freshwater fish in China. However, because of the lack of effective control measures and the high-density culture environment, considerable economic losses are caused by infection of C. idella with the parasitic ciliate, Ichthyophthirius multifiliis. The major histocompatibility (MH) DAB gene belongs to antigen-presented genes in the class II genomic region, which is associated with parasite resistance. To understand the relationship of the DAB gene with I. multifiliis infection in grass carp, the expression profiles of MH II-DAB were studied in tissues using real-time quantitative polymerase chain reaction. The results showed that expression of the MH II-DAB gene was up-regulated in head kidney after I. multifiliis infection, and the expression peak appeared earlier in the study (case) group than in the control group. The obvious up-regulation peak of MH II-DAB gene was found at days 2 and 4 in skin; at 12 h to day 4 in spleen; at 12 h and days 1 and 6 in gill; and at day 10 in blood, whereas the MH II-DAB gene was down-regulated in liver and intestines after I. multifiliis infection. These results have implications for better understanding C. idella resistance to I. multifiliis infection.