Background Chronic epilepsy patients often experience cognitive impairment, and hyperphosphorylation of Tau protein, a feature of neurodegenerative disorders, may be linked to this comorbidity. Levetiracetam (LEV), an antiepileptic drug, improves cognitive function in epileptics, but the mechanism is unknown. This study investigated LEV’s effects on cognitive function and Tau phosphorylation in rats with epilepsy induced by kainic acid (KA). Methods Rats were divided into Sham, KA, and LEV treatment groups (100mg/kg and 300mg/kg, immediately or after 4 weeks). Morris water maze, Nissl staining, immunohistochemistry, and immunoblotting were used to assess cognitive function, neuronal damage, Tau protein levels, and GSK-3β expression. Results Compared with the KA group, the escape latency of KA+LEV300M was shortened (P<0.01), the residence time in the target quadrant was prolonged (P<0.01), and the exploration distance in the target quadrant was extended (P<0.01). The results of Nissl staining showed that compared with the KA group, the morphology and number of Nissl bodies in the hippocampal regions of KA+LEV300M group were significantly improved (P<0.05). The immunohistochemical results showed that compared with KA group, the AT8 level in KA+LEV300M group (P<0.001) was significantly decreased. Compared with KA group, Tau protein phosphorylation level in KA+LEV300M group was significantly decreased (P<0.05). Compared with KA group, phosphorylation level of GSK-3β at Ser9 site in KA+LEV300M group increased significantly (P<0.01). Conclusion LEV reversed KA-induced hyperphosphorylation of Tau protein in chronic epileptic rats by inhibiting the activity of GSK-3β in the brain, thus improving the cognitive function of chronic epileptic rats.