In this study, we demonstrated that levels of soluble MD-1 markedly increased with disease progression in sera from MRL/lpr mice. To identify potential sources of serum soluble MD-1 in MRL/lpr mice, we measured the expression of MD-1 mRNA in the spleen, liver and kidney. In the liver and kidney of MRL/lpr mice, levels of MD-1 mRNA increased with age. Furthermore, the expression levels of MD-1 protein in the kidney of MRL/lpr mice increased with age. Finally, we investigated the cell types responsible for MD-1 expression in the kidney of MRL/lpr mice by immunohistochemical analyses. H & E staining of kidney sections revealed that Mac-2-positive macrophages accumulated in the perivascular lesions even at an early stage. More accumulated macrophages were observed in kidneys of 24-week old MRL/lpr mice than 8-week old ones. These cells were also stained with anti-MD-1 polyclonal antibody. These results suggest that macrophages in the kidney express MD-1 and might be a source of serum soluble MD-1 in MRL/lpr mice.