Galectin-3 (Gal-3) is a member of a class of carbohydrate-binding proteins and plays a role in a number of cellular functions such as cell proliferation, angiogenesis and differentiation. We observed an up-regulated expression of Gal-3 in the ischemic brain following transient middle cerebral artery occlusion in rats. Compared to the brain of sham-operated rats, the expression of Gal-3 was increased in the ischemic striatum at day 1 of reperfusion. The number of Gal-3+ cells in the ischemic brain was further increased at day 2 and day 3, and peaked at day 7 of reperfusion. The up-regulated expression of Gal-3 persisted from day 14 to 2 months after reperfusion. Double staining showed co-localization of Gal-3 with OX-42+ cells, glial fibrillary acidic protein (GFAP)+ and ED1+ cells, suggesting that activated microglia/infiltrating macrophages and activated astrocytes are the primary source of Gal-3 in the ischemic brain. In the in vitro setting, Gal-3 treatment dose-dependently stimulated the proliferation of endothelial cells and neural progenitors. Blockade of Gal-3 activity by infusing a neutralizing antibody against Gal-3 into the ischemic striatum decreased ischemia-induced angiogenesis and the proliferation of neural progenitors. These results suggest that Gal-3 expressed by activated microglia/infiltrating macrophages and astrocytes in the ischemic brain may play a role in post-ischemic tissue remodeling by enhancing angiogenesis and neurogenesis.