Background Anxiety is a negative emotional response associated with the perception of ambiguous stimuli. Depression and anxiety enhance seizure frequency. Epileptic seizures also showed anxiogenic effects in clinical and experimental observations. Early life febrile seizures -FS- enhanced anxiety behaviors. Anxiety is mediated by alteration of different receptors -orexin, kainate and GABA receptors- in experimental animals. Previous studies showed that targeting peroxisome proliferator-activated receptor gamma -PPAR-γ- offered novel strategies as an anxiolytic substance. Researches emphasized that PPAR-γ has the ability to modulate anxiety-related behaviors. On the other hand, activation of PPAR-γ, by pioglitazone -PGZ-, PPAR-γ agonist, reduced inflammation and exerted anxiolytic effect in some human psychologic patients. The aim of this study was the evaluation of pioglitazone effect on rat pups undergone febrile seizures. . Methods Male wistar rat pups were divided into four experimental groups. Febrile seizures were induced by hyperthermia. All pups at day 8 -P8-, were treated with three different doses of PGZ -5, 10, and 20 mg/kg, i.p.- till day 12 -P12-. They also received PGZ from day 13 -P13- till day 17 -P17-. Negative control group was given just normal saline. At the end of experimental protocol, the elevated-plus maze -EPM- test was done. Results According to recorded behaviors in EPM criteria, results showed significant effect of PGZ on anxiety behaviors -open arm entries -%-, open arm times -%-, and total arm entries compared to Control group. Conclusion The present results indicated that pioglitazone had ameliorative effects on anxiety-related behaviors induced by febrile seizure in rat pups.

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