Spleen T-lymphocytes, especially CD4(+) T-cells, have been demonstrated to be involved in broad immunomodulation and host-defense activity in vivo. Apolipoprotein M gene (apoM) may have an important role in the regulation of immunoprocess and inflammation, which could be hypothesized to the apoM containing sphingosine-1-phosphate (S1P). In the present study we demonstrate that the splenic CD4(+) T-lymphocytes were obviously decreased in the apoM gene deficient (apoM(-/-)) mice compared to the wild type (apoM(+/+)). Moreover, these mice were treated with lipopolysaccharide (LPS) and it was found that even more pronounced decreasing CD4(+) T-lymphocytes occurred in the spleen compared to the apoM(+/+) mice. The similar phenomena were found in the ratio of CD4(+)/CD8(+) T-lymphocytes. After administration of LPS, the hepatic mRNA levels of tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) were markedly increased; however, there were no statistical differences observed between apoM(+/+) mice and apoM(-/-) mice. The present study demonstrated that apoM might facilitate the maintenance of CD4(+) T-lymphocytes or could modify the T-lymphocytes subgroups in murine spleen, which may further explore the importance of apoM in the regulation of the host immunomodulation, although the detailed mechanism needs continuing investigation.