Objectives: In this study, we aim to reveal the alterations (due to seizure) in the serum and brain levels of nesfatin-1, ghrelin and irisin after acute or chronic pentylenetetrazole administrations in rats using sodium valproate. Methods: 35 Wistar albino rats were randomly divided into five groups: Control, Acute Pentylenetetrazole group (APTZ), Acute Pentylenetetrazole+ Valproate group (AVPA), PTZ kindling group (PTZk) and PTZ kindling+ Valproate group (KVPA). Serum and brain levels of ghrelin, nesfatin-1 and FNDC5/irisin were determined with ELISA. Results: Serum levels of ghrelin were significantly decreased in APTZ and PTZk groups compared to the control (p < 0.01). There was a statistically significant decrease in brain levels of ghrelin in all groups compared to the control group (p < 0.01). There was a statistically significant increase in serum nesfatin-1 levels in the APTZ and PTZk groups compared to the control (p < 0.05). Serum levels of nesfatin-1 were similar to the control group in both the acute and the chronic treatment groups. There was a statistically significant increase in brain nesfatin-1 levels of the KVPA group compared to the control (p < 0.05). Serum and brain levels of FNDC5/irisin were found significantly increased in APTZ, AVPA and PTZk groups compared to the control (p < 0.01). Conclusions: Statistically significant alterations were detected in the serum and brain levels of these three peptides in both the PTZ-induced chronic epilepsy model and acute seizure model. The results of this study may suggest that the increase in FNDC5/irisin and nesfatin-1 levels, and the decrease in ghrelin levels may contribute to seizure pathophysiology. However, further studies are needed in order to confirm our hypothesis.