Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of epilepsy. The potential neuroprotective effect of curcumin (CUR) on KA-induced epilepsy in mice was evaluated. 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+ CUR protected group) mice received CUR (200 mg/kg b.wt/day/orally) for 7 days before KA administration. Group IV:(epilepsy+ CUR treated group): mice first injected with KA(10 mg/kg b.wt/i.p.) then after 15 min. CUR was administered as in group III for 3 consecutive days. The obtained results showed that, KAinduced 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 , IL-1β and brain tissue nitric oxide NO, L-MDA levels, caspase-3, DNA-fragmentation, 8-hydroxy-2-deoxyguanosine 8-OHdG, activator protein-1 activator protein-1 AP-1 and Myeloperoxidase MPO were significantly increased. Administration of CUR was able to mitigate KA- induced epilepsy through rising of serum SA and brain tissue enzymatic antioxidants status and GSH and declining NO, LMDA, caspase-3, DNA-fragmentation, 8-OHdG, AP-1 and MPO in brain tissue. The microscopical examination of brain tissues obtained from rats injected with KA showed variable pathological changes represented mainly in hemorrhage, edema, neural degeneration and encephalomalacia. Meanwhile, curcumin injection was able to reduce the severity of these alterations with variable degree especially in epilepsy+curcumin treated group. These results suggest that, CUR may be successful in the treatment of epilepsy by its radical scavenging, anti-inflammatory and antiapoptotic activities and regenerating endogenous antioxidant mechanism. Also, curcumin protects mice brain against KA induced neuronal damage, decrease the severity of epilepsy and attenuated kainite induced inflammation and apoptosis.