M-T7 is a myxoma virus-encoded protein that has been found to bind and disrupt human chemokine gradients. This study examined whether purified M-T7 could prevent chronic rejection in a rat renal allograft model. Fisher F344 renal allografts were transplanted into Lewis rats. Recipients were randomly grouped into two groups: control animals treated with cyclosporine alone and animals treated with cyclosporine combined with low-, medium- and high-dose M-T7 viral protein. The survival rate was not significantly different between allograft groups. Renal allografts treated with high-dose M-T7 demonstrated a significant reduction in tubular atrophy, glomerular atrophy, vascular hyalinization, cortical scarring, and lymphocyte infiltration. Morphometric analyses demonstrated that the high-dose M-T7 group also showed a significantly decreased amount of glomerulosclerosis and transplant arteriosclerosis. These data demonstrate for the first time that the immunoregulatory viral protein M-T7 can effectively attenuate chronic rejection in rat renal allografts.