PD-L2, a newly identified member of B7 family, plays a role in down-regulating T cell responses. The common PD-L2 mRNA (type Ⅰ) is the splicing product containing all 6 exons. We report here the identification of two human PD-L2 splice variants in activated leukocytes. One splice variant (type Ⅱ) is generated through splicing out exon 3 encoding Ig constant-like domain; it retains all other regions without a frame shift. The other variant (type Ⅲ) is created by splicing out exon 3 to an alteative acceptor site 5 bp downstream of the canonical acceptor site, leading to a frame shift. Consequently, the translated protein should be a soluble form. Furthermore, type Ⅰ isoform is expressed on the plasma surface whereas type Ⅱ isoform showed a patte of intracellular membrane distribution in the transiently transfected K562 cells. In addition, the expression pattes of PD-L2 splice variants are variable in different individuals and distinct cellular status. These results suggest that PD-L2 expression may be controlled by posttranscriptional regulation through alteative splicing, and modulation of PD-L2 isoform expression may influence the outcome of immune response.