Abstract Cellcept® inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation and suppresses antibody formation in B-lymphocytes. MPA prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in adhesion to endothelial cells. Although Cellcept® is prescribed "off label" to treat SLE and shows great benefits, the exact mechanism of action is not fully understood. MRL/lpr developing glomerular disease mice that exhibit similar pathology to human SLE were used to study the therapeutic effects of Cellcept®. Although Cellcept® at 100mg/kg doses significantly decreased the proteinurea levels in the treated mice, it had marginal effects on the ds-DNA antibody levels. In addition, Cellcept® reduced the levels of B cells in the spleens of treated mice consistent with its immunosuppressant benefit. Histopathological evaluation demonstrated that Cellcept® reduced glomerulonephritis but not vasculitis in kidneys of treated mice. Furthermore, it was shown that Cellcept® lowered the number of monocytes in kidneys; this is the most likely mechanism of action responsible for the less kidney damage and lower proteinurea levels. The reduction in the number of monocytes in kidneys is the first major indication that the beneficial effect of Cellcept® to the kidney function in patients with SLE might be due to the inhibition of mocnocyte infiltration responsible for the destruction of nephritic tissues and not through the action on B cells by lowering the ds-DNA antibody levels.