It was previously reported that females with proestrous are more susceptible to picrotoxin-induced epileptic seizures than males, provided that the estrous cycle is taken into consideration (Tan & Tall, 2001). The sex difference in susceptibility to picrotoxin-induced seizures was reconsidered in the present study using rats with a previous octreotide (a stable somatostatin analogue) injection, as somatostatin is known to be involved in epileptic, phenomena. Contrary to rats without octreotide, males were more susceptible to picrotoxin-induced seizures than females. Statistical analysis indicated that only males showed decreased latencies to seizures and increased seizure frequencies following Octreotide; females were not affected by this experimental procedure. It was suggested that as a GABA antagonist, somatostatin may contribute to the occurrence of epileptic discharges in nervous system, creating a sex difference to epileptic seizures. These results may have implications for understanding the epileptic mechanisms, with possible therapeutic consequences.