Compositions and methods for treating transplant rejection in a mammalian transplant recipient are provided. The method involves administering a therapeutically effective amount of Serp-1, its analogs, and biologically active fragments thereof in combination with an anti-rejection agent, such as cyclosporin, and a pharmaceutically acceptable carrier to a subject in need of such treatment. The compositions and methods are useful for treating acute and chronic allograft and xenograft transplant rejection in mammals.