Here, we show for the first time that activation of the EP4 receptor with L-902,688 given at the onset of reperfusion significantly reduces infarct size, blood-brain barrier (BBB) breakdown, MMP-3 and MMP-9 levels, degradation of tight junction proteins, and stroke-induced increase in the expression of the pro-inflammatory cytokines IL-1β and IL-6. This evidence concerns the gene MMP3 and stroke disorder.