Obesity is linked to more deaths worldwide. In obesity, there will be a dysregulation of growth signals such as tumorigenesis. Despite the fact that obesity is tend to progress to acute liver damage, not many study using 2-nitropropane (2NP) as a hepatoxicity agent  are undertaken  especially in obese mice.This study aimed to determine the regime of 2NP that causes acute liver damage. This is an experimental research using a post-test control design group only, with 3 groups of mice ie O1 (obesity), O2+2-NP1x (induced by 2NP 100 mg/kg BW once), and O2+2-NP2x (induced by 2NP 100 mg/kgBW  twice). At 10 weeks, rats were sacrificed and 100 mg liver tissue were collected for MDA, GSH, MnSOD and CAT enzymes analysis. Analysis statistics were performed by SPSS by one-way Anova and post hoc Tukey.MDA levels of mice were found to be increased in 2NP group than control (3.768 ± 0.407 nmol/mg) (p < 0,01).  Liver GSH, MnSOD and CAT levels of both single injection 2-NP and  repeated injection 2-NP groups decreased compared to those of controls (p<0,01). Repeated injection of 2-NP worsen the acute liver damage in obese mice.