Introduction: Epilepsy is characterized by recurrent unprovoked seizures and affects 0.5-1% of people worldwide. More than 30% of the epilepsy patients have uncontrolled seizures or unacceptable medication-related side effects despite adequate pharmacological treatment. The use of plant extracts to treat diseases is proposed as a therapeutic modality. Datura plant has been used in traditional medicine for treatment of some neurological disorders, like epilepsy. The aim of this investigation was to test Datura on an intractable experimental model of epilepsy. Materials and Methods: 40 adult mice were randomly divided into 5 groups including: control group, sham group, and three treatment groups. Doses of 100, 200, and 400 mg/kg body weight of aqueous extract of Datura stramonium seed were gavaged in treatment rats for 24 days. Chemical kindling was produced by intraperitoneal injection of 45 mg/kg pentylenetetrazole (PTZ) once every 48 hours for 12 times to induced seizure after 30 minutes of gavage in sham and experimental groups. The latency of seizure onset, the duration of the seizure, and the intensity of seizure were measured. Results: Data analysis indicated that the equeous Datura stramonium L seed extract had a significant effect on PTZ-induced seizure. This herb increased the latency of seizure onset, decreased the intensity of seizure attacks, and reduced seizure duration. Conclusion: The present data indicated that extract of Datura stramonium has anticonvulsant effect on PTZ-induced seizure. This finding points to its potential therapeutic effect in epilepsy.