We performed molecular phylogenetic analysis of MHC class II DRB genes among the Japanese weasel (Mustela itatsi), a species endemic to Japan, the Siberian weasel (Mustela sibirica), a closely related species on the continent, and the least weasel (M. nivalis), widely distributed in the Holarctic, including Japan. The 242-bp region of exon 2, which encodes antigen binding sites, were sequenced and found 24 sequences representative of DRB alleles from 31 M. itatsi individuals, 17 alleles from 21 M. sibirica individuals, and 28 alleles from 35 M. nivalis individuals, including broadly distributed, species-specific and/or geographically restricted alleles. In addition, MEME analyses demonstrated positive selection sites that could be committed to maintain the diversity of the DRB alleles. According to the reconstructed Bayesian phylogenetic tree, all alleles from M. itatsi, M. sibirica, and M. nivalis were grouped within the Mustelidae clade. Some alleles from the other species are more closely related to one another than to alleles from the same species, the DRB alleles obtained in this study showed trans-species polymorphism in related Mustela species, that could have appeared to be evolved under long-lasting balancing selection. However, the sister-group patterns suggested that M. itatsi and M. sibirica alleles are much more closely related to one another than either are to M. nivalis alleles (Nishita et al., 2015 and in press). This result correlates with the large genetic distance separating M. nivalis from M. itatsi or M. sibirica, data for which we have previously reported based on mtDNA sequences (Kurose et al., 2000).