Abstract: Background and Objective: It has been proven that intravenous anaesthetics have a good analgesic effect without causing any respiratory system side effects. In this experimental study, we scrutinized the neuroprotective effect of thiopental sodium against Isoflurane (ISO) induced cognitive dysfunction in rats. Materials and Methods: ISO was used to induce cognitive dysfunction in rats and rats were treated with thiopental sodium. Neurochemical parameters including Brain-derived Neurotrophic Factor (BDNF), Acetylcholine (Ach), Choline Acetyltransferase (ChAT), Acetylcholinesterase (AchE), amyloid-β peptide and protein carbonyl were determined. Antioxidant parameters and inflammatory mediators were estimated. Results: Thiopental sodium treated rats exhibited increased latency time, transfer latency time and decreased escape latency time. Thiopental sodium treated rats boosted the levels of Ach, ChAT and AchE. Thiopental sodium significantly (p<0.001) abridged the level of amyloid β-peptide, protein carbonyl and improved the level of BDNF. Thiopental sodium significantly (p<0.001) suppressed the level of MDA and boosted the level of SOD, GPx and CAT. Thiopental sodium significantly (p<0.001) down-regulated the levels of TNF-, IL-4, IL-1, IL-6, IL-10 and increased the levels of IL-2. Conclusion: Overall, thiopental sodium had a neuroprotective effect against ISO-induced cognitive impairment by altering oxidative stress and inflammatory responses.