Introduction: Spreading depression (SD) is a bioelectrical event in the central nervous system and involves in the pathophysiology of some neurological disorders. In this present study, we indicate enhancement of long-term potentiation of hippocampus tissue in juvenile rats faced to cortical spreading depression repetitively. Materials and Methods: Silver recording electrodes as well as a cannula were implanted over the brain of juvenile rats. Repetitive cortical SD events were induced by KCl 3 M weekly injection through the cannula. The brains were removed after 4 weeks. Transverse sections were prepared and incubated in artificial cerebrospinal fluid. Single electrical stimulations were applied through a bipolar electrode placed on to the hippocampal Schaffer collaterals. The field excitatory postsynaptic potentials (fEPSP) were elicited by adjusting the intensity of stimulation to 50% of that at which population spikes began to appear. Results: Repetitive SD enhanced the long-term potentiation in CA1 hippocampal area. The data indicate that repetitive cortical SD in juvenile rats significantly increases the amplitude of the fEPSP form the baseline. Conclusion: This may clarify the pathophysiology of memory deficit were seen in some neurological disorders in children.