Curcumin (Cur) is a major active component of the food flavor turmeric isolated from the powdered dry rhizome of Curcuma longa Linn., which has been used in traditional Chinese medicine to ameliorate intracerebral ischemic damage and reduce brain edema. However, the effects of Cur on the disruption of the blood-brain barrier (BBB) induced by brain ischemia are still unclear. The effects of Cur on the disruption of BBB and changes of tight junction (TJ) proteins induced by oxygen glucose deprivation (OGD) were studied in BBB in vitro. The transendothelial electrical resistance and the flux of horseradish peroxidase in BBB in vitro were measured. The expression and localization of the TJ proteins occludin and zonula occludens-1 (ZO-1) were evaluated by Western blots and immunofluorescence microscopy. The protein levels of heme oxygenase-1 (HO-1) were also analyzed via Western blots. Cur attenuated OGD-induced disruption of paracellular permeability and increased the expression of HO-1 protein in rat brain microvascular endothelial cells (RBMECs). After administration of OGD, the expression of occludin and ZO-1 proteins was restored by Cur, and this effect was blocked by a HO-1 inhibitor, zinc protoporphyrin (ZnPP). Cur protects RBMECs against OGD-induced disruption of TJ and barrier dysfunction via the HO-1 pathway. We propose that Cur is capable of improving the barrier function of BBB under ischemic conditions and this beneficial effect might be reversed by a HO-1 inhibitor, ZnPP.