Objective To study the bidirectional effects of 7-nitroindazole on focal cerebral ischemia-reperfusion injury in rats, and preliminarily investigate the cause of this phenomenon. Methods Healthy male SD rats, 8-10 weeks old, 250-280g. The rat model with temporary focal cerebral ischemia was established by rat middle cerebral obstructed(MCAO). Animals were randomly divided into 4 groups(n=6, each): sham group(Sham Group), cerebral ischemia-reperfusion + DMSO group(Vehicle Group), cerebral ischemia-reperfusion + 7-NI 75mg/kg + DMSO group (High Dose Group), cerebral ischemia-reperfusion + 7-NI 25mg/kg + DMSO group(Low Dose Group). Four hours after occlusion, the rats of vehicle group were injected intraperitoneally with 10% DMSO, while the high dose group and low dose group were administrated with 75mg/kg 7-NI and 25mg/kg 7-NI respectively. Neurobehavioral scores were evaluated at the time points of 2h, 4h, 24h after focal cerebral ischemia. Then rats were sacrificed to detect the level of NO, activity of NOS and cerebral infarction volume. Results Compared with sham group, neurobehavioral scores after occlusion were significantly increased and NO level and nNOS activity were significantly increased in vehicle and high dose group(P<0.05). Compared with vehicle group, in high dose group, neurobehavioral scores after occlusion were increased, NO level and nNOS activity were significantly reduced, and cerebral infarction volume was significantly increased; in low dose group, neurobehavioral scores after occlusion were reduced, NO level and nNOS activity were significantly reduced, and cerebral infarction volume were significantly reduced. Compared with high dose group, NO level and nNOS activity in low dose group were significantly increased(p<0.05). Conclusion After cerebral ischemia-reperfusion, administration of 7-NI has a protective effect at low dose while a damage effect at high dose, which may due to the basic physiological role of nNOS in injured cells.