Epilepsy is one of the most common neurological disorders characterized by epileptic seizures that affect a man’s health and social life. Valproic acid (VPA) is a well-known antiepileptic drug but still has adverse effects on different organs including the brain. Taurine (Tau) is one of the most abundant amino acids in the brain and has an essential role in neural stem/progenitor cell proliferation. The present study aims to determine the potential adjuvant role of Tau on improving the anti-epileptic properties of VPA in the pentylenetetrazole (PTZ) epileptic model. Forty-two rats were divided into 6 groups: control group, PTZ-treated group (single i.p. dose 60 mg/kg), VPA group (i.p. 500 mg/kg for 14 days), Tau-treated group (100 mg/kg oral for 28 days), VPA+PTZ group, and Tau+VPA+PTZ group. PTZ injection induced epileptic seizures and triggered deleterious changes in the aminergic system of the cortical and hippocampal tissue of the rat’s brain. Compared with PTZ-epileptic rats, the pre-treatment with VPA showed a significant delay in seizure start and a significant decrease in its duration and partially improved the aminergic system of the cortical and hippocampal tissues of the rat’s brain. The combination of Tau and VPA as a pre-treatment revealed a significant decrease in seizure duration, seizure intensity and significantly restored the concentration of free amino acids, monoamines, and its metabolites in the cortex and the hippocampal regions of the rat brain as compared to the group pre-treated with VPA alone. In conclusion, the use of taurine with valproic acid as an adjuvant therapy is highly recommended in order to control neurological epileptic changes induced by PTZ in rats.