Galectin-1 (Gal-1) is a β-galactoside binding protein, the expression of which is increased in endothelial cells upon exposure to pro-inflammatory stimuli (Baum LG et al. 1995). Through binding of several receptors (CD7, CD45 and CD43) Gal-1 is known to induce apoptosis of activated T lymphocytes, an effect thought to mediate the beneficial effects of Gal-1 in various inflammatory models. The data presented here highlights another function for Gal-1; that of a negative regulator of T cell recruitment to the endothelium, both under physiological and pathophysiological conditions. We have shown, using siRNA to knockdown Gal-1 in endothelial cells, that endogenous Gal-1 limits T cell capture, rolling and adhesion to activated endothelial cells under flow. Indirect binding and inhibitor studies suggest that Gal-1 acts on CD45 and consequently causes inhibition of the src kinase p56Lck to bring about its inhibitory effect on lymphocyte adhesion. These findings are corroborated by studies in Gal-1 null mice in which homing of wild type T lymphocytes is significantly increased to mesenteric lymph nodes and to the inflamed paw in a model of delayed type hypersensitivity. In conclusion, mimicking endothelial Gal-1 actions would be a novel strategy for controlling aberrant T cell trafficking, hence for the development of anti-inflammatory therapeutics.