Objective To study the antioxidant and antiapoptotic effects of U-74389G on ischemic brain in rats. Methods Right focal cerebral ischemia and reperfusion was induced by suturing in 103 male SD rats weighing 280-310 g. To determine LPO in the cortex and striatum, we randomly divided 78 rats into 5 groups: group 1, sham-operative group (6 rats); group 2, control (18); group 3, U-74389G admi-nistration before ischemia (18); group 4, U-74389G administration before reperfusion; group 5, CS-4 vehicle as negative control. Groups 2-5 were further divided into 3 subgroups according to the duration of reperfusion. Another 25 rats were similarly grouped (5) to detect apoptosis with TUNEL stain. Results The concentrations of MDA in groups 3 and 4 were reduced and the activities of SOD and concentrations of GSH were partially restored as compared with the control group. These effects were more significant in group 3 than in group 4. Otherwise, CS-4 can not provide protective effects. The number of apoptotic cells in groups 3 (P<0.01) and 4 (P<0.05) was significantly reduced as compared with the control group.Conclusions U-74389G has antioxidant and antiapoptotic effects on ischemic brain in rats. The administration of U-74389G before the onset of ischemia was more useful than that before the onset of reperfusion.