Previous studies have demonstrated that (-)-epigallocatechin gallate (EGCG), a green tea polyphenol, protects against ischemia and reperfusion-induced injury in many organ systems. Here, we test the hypothesis that part of EGCG's neuroprotective effects may involve a modulation of matrix metalloproteinases (MMPs) after cerebral ischemia. C57BL/6 mice were subjected to 20 min of transient global cerebral ischemia. EGCG (50 mg/kg) or vehicle (saline) was administered i.p. immediately after ischemia. Brains were examined 3 days after ischemia. The effects of EGCG on MMP (gelatinase) activity and neuronal damage in the hippocampus were assessed. Gelatin gel zymography showed induction of active forms of MMP-9 protein after transient global cerebral ischemia. In situ zymography showed that ischemic gelatinase activity occurred primarily in pyramidal neuronal areas after brain ischemia. Mice treated with EGCG showed significantly reduced gelatinase levels. Neuronal damage was evident in CA1 and CA2 pyramidal sectors, corresponding to TUNEL-positive signals. In EGCG-treated mice, delayed neuronal damage was significantly reduced compared with vehicle-treated mice. These results demonstrate that the green tea polyphenol EGCG suppresses MMP-9 activation and reduces the development of delayed neuronal death after transient global cerebral ischemia in mouse brain.