Chronic allograft dysfunction remains the major obstacle for long-term successful transplantation. To date there is no effective treatment. Overexpression of protective genes has provided increased graft function and survival. This mechanism has been implicated in the process of graft accommodation. One of these genes that has been shown to mediate protective effects decodes the enzyme heme oxygenase-1 (HO-1), and an HO-1 downstream product, carbon monoxide (CO). Using an established model of kidney chronic allograft rejection in the rat, we investigated the impact of methylene chloride (MC), a CO donor, as a therapeutic tool to reduce chronic graft deterioration. We showed that donor and long-term recipient treatment with MC improved graft function and reduced histological signs of chronic rejection. Carbon monoxide may be a promising agent to improve graft quality and long-term graft function.