The objective of the present study was to investigate the ability of n-butanol extract obtained from flowers of endemic Algerian specie belonging to the family of compositae (Chrysanthemum fontanesii) and vitamin E to modulate valproic acid-Induced hepatotoxicity and oxidative damage in pregnant mice. Valproic acid (VPA), a common treatment of epilepsy and other diseases, is known to have severe toxic effects on liver both in experimental animals and in humans. In this present study, we investigated the prooxidant effect of VPA and its implication on hepatic cells. VPA injection in mice at dose of 300 mg/kg induced hepatic dysfunction revealed by a significant increase in serum of AST and ALT. Oxidative stress in liver cells was induced by VPA since a significant reduction of GPx activities and GSH levels, and significant increase of MDA level were observed. The protective effect of vitamin E (100 mg/kg) and n-butanol extract (100 mg/kg) against oxidative stress induced by VPA was also investigated. Indeed, the pretreatment of mice with n-butanol extract protected liver cells from oxidative stress permitting the prevention of hepatic dysfunction on maintaining the normal level of serum transaminases, preventing lipid peroxidation and maintaining antioxidant defense system. Histopathological observations also correlated with the biochemical parameters. These phenolic compounds have also antioxidant power that confers them protection against oxidative stress generated in liver by VPA. The In vitro study confirmed the potential of this extract as antioxidant using DPPH method.