This study intended to investigate the therapeutic effect of ethanolic extract of Tylophora villosa leaves (E2TL) against paracetamol (PC)-induced hepatotoxicity (PCIH) in mice ( Mus musculus ). PCIH were generated using daily 250 mg/kg body weight (bw) PC administration by gavage for seven days, and then daily 27.5; 55.0; 82.5; 110.0; or 220.0 mg/kg bw E2TL were treated by gavage for seven or fourteen days. Meanwhile, the controls were given solvent only in the same manner. Mortality, blood glucose, and condition (color, weight, volume) of the livers were observed on day 15 (D15). Serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SG0T) were examined on D15, D22, and D30, and then malondialdehyde (MDA) was determined on D15. Results of this study revealed that on D15, the dosage of 110.0 mg/kg bw E2TL most effectively decreased MDA due to PCIH, from 6.78 ± 1.70 μmol/L to 3.45 ± 0.43 μmol/L, approaching the control condition (2.45 ± 0.05 μmol/L). PC administration was really toxic dosage and caused 13.3 % mortality. Blood glucose, weight, and volume of the liver decreased as the effect of PC administration, and then 220.0 mg/kg bw E2TL treatment could recover the condition as well as the controls. Color of the liver indicated a similar recovery by E2TL treatment. SGPT and SG0T increased significantly by PC administration, and this PCIH facts could be recovered gradually near the controls according to the dosages (55.0; 110.0; or 220.0 mg/kg bw) and duration (seven or fourteen days) of E2TL treatment. It could be concluded that E2TL showed therapeutic effect against PCIH in M. musculus .