The major histocompatibility complex (MHC) is one of the most important genetic systems associated with resistance to infectious diseases in vertebrates. The spotted seal (Phoca largha) is one of the most endangered species in China. In this study, we present the first step in the molecular characterization of a DRB-like locus in the spotted seal by analyzing the nucleotide sequence of the polymorphic exon 2 segments, a 288-nucleotide sequence. By examining the segment from a group of 41 individuals, 28 alleles were identified. No deletion, insertion, or exceptional stop codon was detected, suggesting that these alleles could be functional in vivo. The nucleotide and amino acid sequences of the segment both showed a relatively high level of similarity (nucleotides 97%; amino acids 98%) to those of Meles meles and Zalophus californianus. The high level of spotted seal MHC-DRB polymorphism revealed in the present study has not been reported for the Phocidae and could be a consequence of the small spotted seal population adapting to the Bohai Sea, which probably has a relatively high level of pathogens.