Background. Initial insults to kidney allografts, character-ized by infiltration of mononuclear inflammatory cells, contribute to chronic allograft nephropathy. Chemokines such as RANTES (regulated upon activation, normal T cell expressed) are thought to be responsible for the recruitment and activation of infiltrating cells. The present study investigated whether early application of Met-RANTES, a chemokine receptor an-tagonist that blocks the effects of RANTES, can protect renal allografts from long-term deterioration. Methods. Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients and treated with cyclopo-rine A (1.5mg/kg/day) for the first 10 days following trans-plantation, together with either Met-RANTES at 40g/day, 200g/day or vehicle for the first 7 days. Animals were har vested at 2 and 28 weeks after transplantation for histologic, immunohistologic and molecular analysis. Results. Met-RANTES treatment reduced the infiltration of belymphocytes and macrophages in allografts at 2 weeks after transplantation, accompanied by decreased mRNA expression of interleukin (IL)-2, IL-1, tumor necrosis factor-(TNF-) and RANTES. At post-transplantation week 28, Met-RANTES treatment at high and low doses reduced urinary protein excre-tion and significantly ameliorated glomerulosclerosis, intersti-tial fibrosis, tubular atrophy, intimal proliferation of graft arter-ies and mononuclear cell infiltration. However, creatinine clearance was not influenced by Met-RANTES. Furthermore, Met-RANTES suppressed the mRNA expression of trans-forming growth factor-(TGF-) and platelet-derived growth factor-B (PDGF-B). Conclusions. Blockade of chemokine receptors by Metby RANTES diminishes early infiltration and activation of mono nuclear cells in the grafts, and thus reduces the pace of chronic allograft nephropathy.