Introduction: Spreading depression (SD) is a transient and self-propagating wave of neuronal and glial depolarization, followed by temporary loss of all brain activities. SD has been implicated in migraine and other headaches and can be evoked in experimental animals by electrical or chemical stimulation. It has been shown that repetitive SD produced memory deficits in juvenile rats. The effect of migraine prophylactic drugs on SD has been reported. In the present study, the effect of sumatriptan, a migraine prophylactic drug, on SD-induced memory impairments in juvenile rats was investigated. Materials and Methods: Wistar rats (60-80 gr) were divided into SD, Sham, 0.1 sumatriptan- and 0.5 sumatriptan-treated groups and SD was induced weekly for four weeks by KCl (2 M) application. Sumatriptan (0.1 and 0.5 mg/kg) was also administrated weekly for 4 weeks in treatment groups. Memory retention of passive avoidance learning in rats was evaluated by shuttle box test in different time points. Results: SD significantly increased the initial latency to enter the dark compartment. SD also impaired the retention of the learned tasks. Administration of low dose sumatriptan caused improvement in memory retention 30 minutes after learning, while the high doses could improve the memory 30 minutes, 24 hours and 1 week after learning. Conclusion: This study shows the positive role of sumatriptan in learning and memory impairment induced by repetitive SD.