Background: ADIOL (5-androsten-3β, 17β-diol) is a metabolite of dehydroepinadro-sterone (DHEA) with antioxidant, anti-inflammatory and antiapoptotic effects. Objectives: examine the possible neuroprotective effect of ADIOL against lithium pilocarpine (li-pilo) induced-seizures, behavioral changes and cognitive deficits Methods: 120male mice were divided into six groups, each contain 20 mice which subdivided equally to A for behavioral tests and B for biochemical tests. "Vehicle Group I", "Control Group II "li-pilo", Valproate (VPA) group IІІ (17 mg/kg,i.p). "ADIOL group IV" ADIOL 0.5 mg/kg, "ADIOL group V" ADIOL 1.5 mg/kg "ADIOL group VI" ADIOL 3.5 mg/kg. The animals were observed for the occurrence of spontaneous recurrent seizures (SRS). Open field test, dark light box, acceleration rotarod test and T maze spontaneous alternation were performed. Six mice from each group were euthanized 30 days after pilo injection. Their brains were removed for assessment of oxidant/antioxidant status, anti-inflammatory and antiapoptotic parameters Results: li-pilo produced seizures associated with behavioral changes and cognitive deficits, significant decrease in brain superoxide dismutase (SOD) activity and significant elevation in the brain malondialdehyde (MDA), interleukin1β (IL-1β), nuclear factor-kappa B (NF-КB) and caspase-3 (cap-3) in relation to vehicle group. VPA suppressed seizures concomitant with improvement of behavioral changes but worsen short term memory, significant increase in brain SOD activity and significant decrease in MDA, IL-1β, NF-КB and cap-3 levels in relation to li-pilo model. ADIOL ( 0.5 to 1.5 and 3.5 mg/kg) produced dose dependent decrease in seizures associated with significant improvement of behavioral changes and cognitive deficits, significant increase in brain SOD activity and significant decrease in MDA, IL-1β, NF-КB and cap-3 levels in relation to li-pilo model. Conclusion: ADIOL protects against li-pilo induced seizures, behavioral changes and cognitive deficits due to antioxidant, anti-inflammatory, antiapoptotic effects.