Blood monitoring provides convenient and minimally invasive method to follow-up the patients suffering from epilepsy. For such analysis, Fourier transform infrared (FT-IR) spectroscopy offers rapid, versatile and relatively non-invasive approach which could determine epilepsy induced biomolecular alterations in blood. In the present study, FT-IR spectroscopy combined with chemometrics such as principal component (PCA) and hierarchical cluster analysis (HCA) was used to analyse blood plasma from rats that experienced pentyleneterazol-induced generalized tonic-clonic seizures (GTCS). Spectral analysis was performed on second derivative spectra of plasma samples. The findings showed that when compared to control there were insignificant alterations in intensities and positions of lipid absorptions of GTCS group. However, major spectral changes such as significant increases in the intensities of alpha-helix (1656 cm(-1) and 1547 cm(-1)) and beta-sheet (1656 cm(-1)) structures in proteins were obtained. While PCA and HCA did not show a discrimination based on 3000-2800 cm(-1) region (lipids), these methods successfully classified control and GTCS groups depending on 1730-1480 cm(-1) (proteins), which is further supported by high specificity (85.7%) and sensitivity (100%) values. Consequently, the results suggest that FT-IR spectroscopy with multivariate analyses such as PCA and HCA may serve as a useful tool to investigate biomolecular alterations induced by acute epileptic seizures in blood plasma.