Objective Epileptogenesis, the process by which the brain becomes epileptic, is related to neuroinflammation, hyperexcitability cognitive deficits. Evidence suggests that improving brain inflammation can inhibit the epileptogenesis process and help the emergence of new drugs for the treatment of epilepsy. Therefore, the PTZ kindling model of epilepsy was utilized to assess the neuroprotective role of thiamine in epileptogenesis. Methods Male rats were exposed to PTZ-induced kindling and pretreated with low thiamine (25 mg/kg) or high thiamine (50 mg/kg). Cyclooxygenase (COX-1 and COX-2), interleukin 1-beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and nuclear factor-kappa B (NF-kappa B) concentrations in the brain were analyzed using biochemical assays. Cognitive function was evaluated using the passive avoidance test. Results Thiamine ameliorated epileptogenesis and enhanced the rats' performance in the passive avoidance test. Also, thiamine significantly decreased the level of neuroinflammatory mediators in the brain induced by PTZ. Conclusion These results provide evidence that thiamine alleviates PTZ-induced neuroinflammation and cognitive impairments.