Matricaria recutita L. is a well-known medicinal plant that is suggested as being carminative, analgesic, and anticonvulsant in traditional medicine. In the present investigation the effect of hydro-methanolic percolated extract of this plant on seizure induced by picrotoxin was studied in male mice. This study was performed on animals pretreated with doses of 100, 200, and 300 mg/kg of extract or 40 mg/kg phenobarbital as the reference drug via intraperitoneal injection. After 20 min each animal received 12 mg/kg picrotoxin for induction of seizure. Latency of onset time of seizure, duration of seizure, death latency, and death rate were determined in experimental and control groups. The results showed that latency of the beginning time of seizure was increased in groups that were pretreated with different doses of extract. The most effective dose was 200 mg/kg (P < 0.05). In addition, this dose delayed the time of death in mice (P < 0.01). The extract had no effect on the death rate. The results indicate that the extract of M. recutita possesses suitable effects on seizure induced by picrotoxin, and more experiments are needed in this field.