Background and Aim: The aim of the present study was to investigate the effect of Garlic extract on cortical spreading depression (CSD) specifications as underlying mechanism of aura and subsequent pain in migraine in rats' neocortical slices.Materials and Methods: In this experimental study, CSD was induced in rats' somatosensory cortical slices using two models as follows: first, after KCl microinjection, and washing in CSF with low concentration of NaCl the slices were washed for 60 minutes with garlic extract in different conce ntrations (1, 10, 50, and 100 mmol/L), second, the slices were ex posed to 50 mmol/L garlic extract for 60 minutes. In both methods, induced CSD slices were washed in CSF containing alcohol low concentration. Using extracellular potentials recording, the frequency, amplitude, duration, and propagation velocity of CSD were measured. All data was statistically analyzed.Results: In KCl induced CSF model, the amplitude and after/before ratio (P=0.006) of CSD significantly decreased after superfusion of garlic extract at all concentrations with dose-dependent route. Nonetheless, addition of garlic extract non significantly reduced the duration (P=0.08) and propagation velocity (P=0.4) of CSD. In CSD induction with low NaCl concentration CSF model, addition of garlic extract to the washing solution caused reduction of frequency (P=0.006) and amplitude (P=0.03) of CSD. However, the duration of CSD in this model showed no significant difference after using garlic.Conclusion: Regarding to our results, Garlic is able to suppress CSD phenomenon.