Background: Effects of hypothermia have been demonstrated in experimental animals with cerebral ischemia. Although the exact mechanisms of hypothermic effects are unknown, decrease of the blood-brain barrier (BBB) permeability, inhibition of free radical generation, and anti-inflammatory actions have been suggested. Matrix metalloproteinases (MMPs) may play a role in the hypothermic effect because they are known to mediate neuro-inflammatory responses and BBB breakdown. M e t h o d s: The rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO) and 18 hours of reperfusion. The normothermia group was maintained at 37℃. Moderate hypothermia was induced by maintaining the temperature at 32℃ during MCAO in the intra-ischemic hypothermia (IH) group, and for 2 hours immediately after reperfusion in the postischemic hypothermia (PH) group. The infarction size in coronal slices were measured after 2,3,5-triphenyltetrazolium chloride stain. By gelatin zymography, the activity of MMP-2 and MMP-9 was measured. Evans blue extravasation methods were used to determine the BBB disruption. Results: The infarction size was significantly decreased in the IH group compared to the normothermia group. The MMP-2 and MMP-9 activities in the ischemic hemispheres was significantly decreased in the IH group compared to the normothermia group. In the PH group, only the MMP-2 activity was significantly decreased compared to the normothermia group. Infarction size was significantly correlated with MMP-2 (r=0.688), and MMP-9 (r=0.707) activities. The disruption of BBB was significantly reduced in the IH group compared to the normothermia group. C o n c l u s I o n s: Intra-ischemic hypothermia effectively attenuated ischemic injury. Hypothermia-mediated inhibition of MMP-2 and MMP-9 activities may contribute to this protective effect.