Galectin-1 (Gal-1) is a member of a family of endogenous β-galactose-binding proteins with a role in preventing autoimmune diseases and chronic inflammation. In this study, the involvement of Gal-1 in graft rejection was investigated by using Gal-1-deficient mice (Gal-1−/−). We demonstrate that in the absence of Gal-1, skin grafts are rejected earlier compared with those of WT mice, and that this is due to the role played by CD8+ T cells in graft rejection. The difference in graft survival observed between Gal-1−/− and WT mice was explained by both an increase in the percentage of antigen-specific CD8+ T cells and by preferential secretion of IFN-γ and IL-17 by CD8+ T cells in Gal-1−/− mice compared with WT mice. This study suggests that endogenous expression of Gal-1 contributes to graft survival. The results obtained from the use of mice deficient in Gal-1 also confirm a key role for CD8+ T cells in graft rejection.