Abstract: We cloned 171 sequences of MHC class Ⅱ gene were determined from 41 susceptible and 22 resistant individuals of Cyprinus carpio var. singguoensis. These sequences belonged to 26 alleles, thirteen of which were novel (Cyca-DXA24-Cyca-DXA36). The total length of the sequence was 624 bp, consisting of a 33 bp exon1, a 252 bp exon2, a 285 bp exon3, and a 54 bp exon4. These exons encoded a partial signal peptide, a 1 domain, a 2 domain and a connecting peptide (CP)/partial transmembrane (TM), respectively. The mutation-Prone positions of nucleotide or amino acid sites in 1 domain (55.16%, 79.76%) significantly out number than those in 2 domain (45.96%, 68.42%). The values (= dN/dS) were 5.742 for peptide-binding region (PBR), 0.755 for non-PBR in the 1 domain and 0.592 for the 2 domain, implying that the positive selection pressure probably had occurred in the PBR region of the 1 domain. Cyca-DXA24 (P0.01) was significantly correlated with the carp's resistance to Aeromonas hydrophila, while Cyca-DXA3 (P0.05), Cyca-DXA4 (P0.01), Cyca-DXA6 (P0.05) and Cyca-DXA33 (P0.05) alleles were significantly associated with the fish's susceptibility to the disease. Real-time quantitative PCR demonstrated that MHC II genes were ubiquitously expressed in ten tissues. The expression was up-regulated in kidney, down-regulated in liver and spleen during infection. Our results indicated that the MHC class II gene might play an important role in the immune reactions of C. carpio var. singguoensis.