We observed the distribution of monocyte's changes in damage to renal tissue and the expression of macrophage-derived chemokine (MDC) in MRL/lpr mice. The 8-week-old MRL/lpr mice were randomly assigned to receive either MDC antibodies (n = 6) or placebo (n = 6) at a once-every-other-day dose of 300 μl from week 4. We then quantified the differences in 24-h urine protein and serum creatinine concentrations, performed a histological evaluation of renal tissue and assessed the expression of MDC protein and mRNA between the two groups 4 weeks after treatment was initiated. Antibody-treated mice demonstrated significantly lower urine protein and serum creatinine concentrations and had fewer renal lesions compared with control mice. The expression of MDC protein and mRNA in renal tissues was significantly lower in the antibody-treated mice than in control mice, suggesting that the elevated expression of MDC, which led to monocyte infiltration in the kidney, may play an important role in the development of lupus nephritis. Furthermore, the anti-MDC antibodies may act to alleviate the renal lesions of murine lupus nephritis by inhibiting the infiltration of monocytes in the renal tissue of the lupus mice.