The aim of this study was to evaluate in vivo hepatoprotective activity of the ethanol-water extract of Jatropha gossypiifolia leaves (EJG) against mouse-induced hepatitis (MHV) in Mus musculus mice. This experiment was carried out with 30 male mice, divided into 6 batches, one control non-contaminated and five batches infected with MHV extracted from wild-type mice liver. Four batches of the infected mice were treated with either EJG (75, 150 and 300 mg/kg) or lamivudine (10 mg/kg) used as reference treatment. The fifth infected batch was untreated. The mice of all the batches were monitored every 12 hours for 5 days, including weight measurements and behavioral assessments. After 10 days of the MHV liver extract inoculation, all the subjects were sacrificed, the serum was collected and the biochemical parameters were measured. The results showed that MHV inoculation induced significant increase (p < 0.05) of relative weight of liver, heart, kidney and spleen in negative control, as well as serum values of ASAT, ALAT, C-reactive protein (CRP) and bilirubin compared with the control group. EJG at the concentrations of 75, 150, 300 mg/kg induced a significant reduction (p < 0.05) in relative organ weights, ASAT, ALAT, CRP and bilirubin contents compared with the negative control. In conclusion, EJG could protect the organs and has a potent hepatoprotective effect against MHV-induced liver damage in mice.