Macrophage accumulation is a prominent feature in most types of human glomerulonephritis. In particular, tubulointerstitial macrophage accumulation correlates with the degree of renal dysfunction and is predictive of disease progression. Depletion studies have shown that macrophages can induce glomerular injury in experimental glomerulonephritis. Moreover, recent studies targeting chemokines and adhesion molecules have shown that inhibiting macrophage accumulation can suppress progressive renal injury in animal models of glomerulonephritis. Macrophages can produce many molecules with the potential to cause renal damage, although the precise mechanism(s) of macrophage-mediated renal injury have yet to be determined. It is now evident that tubules-a major source of chemokines and adhesion molecules-play an active role in promoting interstitial macrophage infiltration and activation. Thus, targeting pro-inflammatory functions of tubular epithelial cells may be an effective means to inhibit macrophage-mediated tubulointerstitial injury without causing systemic immunosuppression.