Background: It is demonstrated that morphine and tramadol affects seizure but the mode of action of these drugs on seizure has not been compared yet with increasing of age. The aim of this study was to compare the impact of exposure to these drugs on Pentylenetetrazol-induced seizure in immature rat.Methods: Male neonate rats were randomly chosen and divided into three groups namely Saline (n=21), Morphine (n=12) and Tramadol (n=13). On postnatal days 8-14, Saline group received normal saline and two other groups received morphine and tramadol with additive doses, respectively. On postnatal days 22-28, the saline treated rats divided into three subgroups and received saline (n=8), morphine (n=8) or tramadol (n=5). Morphine treated rats received saline or morphine (each n=6), and tramadol treated rats received saline (n=7) or tramadol (n=6). At postnatal day 29, they were evaluated for PTZ-induced seizure.Results: Number of tonic-clonic seizure was increased in all groups compared with control and tramadol+saline groups (P<0.05). Duration of tonic-clonic seizure was decreased in tramadol+saline group compared with other tramadol groups (P<0.05). Latency of tonic-clonic seizurewas decreased in tramadol+saline group compared with control rats (P<0.05), But it was increased in saline+tramadol group compared with other groups except to saline group (P<0.05). Latency of myoclonic contractions in saline+morphine and saline+tramadol groups was lower than in control rats (P<0.05).Conclusion: Similar age-related changes may occur inchronic exposure to morphine and tramadol in the neonatal period which leads to an increase in severity of seizures in rats on postnatal days 22-28. The effect of morphine and tramadol does not show any significant difference.