Background: Fatty liver is a disease when the accumulation of liver fat reaches 5% of the liver weight. To date, no ideal pharmacological therapy exist yet, so non-pharmacological therapy is still the first therapy given to fatty liver patients. Objective: This research aimed to obtain the animal model of fatty liver condition and to evaluate the administration of pioglitazone in the animal model. Materials and Methods: Animal model study was conducted by oral induction of high-fat diet only and induction of high-fat diet and propylthiouracil every week for 42 days. Furthermore, the animal model was used to evaluate the administration of pioglitazone by using 30 male white rats divided into 5 groups, normal group, negative control group, and three dose variations of pioglitazone (1 mg, 2 mg and 4 mg/200 g BW/day). Pioglitazone is orally administered for 28 days. The parameters of AST, ALT, triglycerides, and liver morphological observations were measured. In addition, measurements of other parameters such as total cholesterol, HDL, LDL, and antioxidant activity, Gpx and SOD, were carried out to evaluate the administration of pioglitazone. Results: The group with induction of high-fat diet and propylthiouracil showed a higher increase in the activity of AST, ALT, and triglycerides compared to high-fat diet only. Furthermore, the administration of pioglitazone gave an increase in the activity of AST, ALT and triglycerides in the first three weeks, but at week 4 (day 28), the activity decreases. Pioglitazone at a dose 2 mg/200 g BW/day showed the highest decrease compared to other doses. Conclusion: This study concludes that propylthiouracil can increase fatty liver so the induction of a high-fat diet with propylthiouracil is better than the induction of a high-fat diet only. The administration of pioglitazone at a dose of 2 mg/200 g BW/day showed the best results compared to other doses.