Background: depakine and epanutin introduce useful tools in wide range of clinical issues. Liver is the localposition for their metabolism and is susceptible for their influences.Methods: forty-two male albino mice were divided into seven groups. control group injected with NaCl(0.9%) 1ml/kg, group 2 injected with depakine 25mg/kg/day, group 3 injected with depakine 50mg/kg/day,group 4 injected with epanutin 3mg/kg/day, group 5 injected with epanutin 6mg/kg/day, group 6 injectedwith (depakine 25 + epanutin 3) mg/kg/day and group 7 injected with (depakine 50 + epanutin 6) mg/kg/day. All animals were injected intraperitoneally, were fasted 12hours after last injection, were sacrificed viacervical dislocation and specimens were collected after one and two weeks for each dose.Conclusions: human therapeutic doses range of depakine and/or epanutin produced elevation in the mean ofliver aminotransferases enzymes levels in serum without dose or time depend and generate variable degreesof hepatotoxicity in mice according to dose and depend on time.