The PKD1L3 gene encodes an ion channel protein that can interact with the PKD2L1 protein to form a candidate sour taste receptor. In the present study, we have analyzed the evolutionary patterns of PKD1L3 genes from 10 mammalian species. The results showed that PKD1L3 genes have evolved under a dominant purifying selection force. However, for some branches and sites, PKD1L3 genes were detected to have been operated by positive selection. Moreover, some of these positive evolutionary sites are likely to participate in acid stimulus recognition. In rodents, PKD1L3 genes evolved more rapidly than other mammalian lineages. Combined with other functional research reports, our results suggest that rodents may not be the most appropriate model for functional research on the PKD1L3 gene.