Epilepsy is a highly prevalent serious brain disorder, and oxidative stress is regarded as a possible mechanism involved in epileptogenesis. The present study was designed to evaluate the potential protective and beneficial effect of resveratrol (RESV) on kainic acid (KA)-induced epilepsy in mice. Twenty four male Swiss Albino mice were divided into four groups. Group Ι: (Control group) mice received no drugs. Group Π: (epilepsy-induced group): mice administered with a single dose of KA (10 mg/kg b.wt) intraperitoneally (i.p). Group III: (epilepsy+RESV protected group) mice received RESV (10 mg/kg b.wt/day/i.p.) for 7 days before KA administration. Group IV: (epilepsy+RESV treated group): mice first injected with KA (10 mg/kg b.wt/i.p.) then after 15 min. RESV was administered as in group III for 3 consecutive days. The obtained results showed that, KA-induced epilepsy in mice caused significant decrease in serum sialic acid (SA) and brain tissue SOD, CAT, GPX activities and GSH concentration. However, serum TNF-α, interleukin-1 beta (IL-1β) and brain tissue nitric oxide (NO), L-MDA level, caspase-3 activity, DNA-fragmentation, 8-hydroxy-2-deoxyguanosine (8-OHdG), activator protein-1 (AP-1) and Myeloperoxidase (MPO) were significantly increased. Administration of RESV was able to mitigate epilepsy induced by KA through increasing of SA and brain tissue SOD, CAT, GPX activities and GSH in addition to declining NO, L-MDA, caspase-3 , DNA-fragmentation, 8-OHdG, AP-1 and MPO in brain tissue. The histopathological examination of brain tissues obtained from rats injected with KA showed variable pathological changes. Meanwhile, resveratrol injection was able to reduce the severity of these alterations especially in group IV (epilepsy+RESV treated group).The present study demonstrated that, RESV.possesses significantly neuroprotection and treatment effects against epilepsy and oxidative damage in brain tissue induced by KA in mice.