Oxidative stress has a crucial role in epileptic seizures. Several studies have shown the protective effect of Artemisia absinthium (A. absinthium) against neuronal damage and oxidative stress. In the current research, the effect of A. absinthium on oxidative stress indicators in an animal model of seizure provoked by injecting pentylenetetrazole (PTZ) was estimated in mice. The mice were allocated into the following groups: a control group in which vehicle was administered; PTZ group (a single dose of 100 mg kg-1, ip); and other groups, which daily received 6.25-200 mg kg-1 of the A. absinthium extract during 3 consecutive days before PTZ. The first recorded MCS and minimal clonic seizure and the first generalized tonic-clonic seizure (GTCS) latencies were analyzed. The brain segments, including the cortex and hippocampus of the animals, were then removed and harvested for oxidative stress evaluation. The extract significantly postponed the onsets of the MCS and GTCS when injected before PTZ. The seizure attacks provoked by PTZ also increased MDA in the cortex and hippocampus to levels greater than the control (P<0.001). In addition, the extract had an ameliorative effect on MDA concentration in the cortex and hippocampus (P<0.05-P<0.001). A lower concentration of total thiol was observed in the brain of the PTZ injected mice than the control ones (P<0.01- P<0.001). Pretreatment with the extract corrected the thiol level in the brain tissue (P<0.05- P<0.001). The current research shows that A. absinthium hydro-ethanolic extract has considerable anti-oxidant properties in a PTZ-induced seizure model in mice. Manuscript profile