BACKGROUND Pioglitazone increases insulin sensitivity and improves glycemic control in type 2 diabetics. In this study, we evaluated the effects of pioglitazone on the uncoupling protein 1 (UCP1) expression in mouse brown adipose tissue (BAT), and on recovery from oxidative stress due to a high-fat diet. METHODS 30 mice were divided into three groups: group 1 received a normal diet, group 2 received a high-fat diet, and group 3 received a high-fat diet plus 30 mg/kg pioglitazone. After treatment, the cholesterol, triglyceride, paraoxonase 1 (PON1), total serum antioxidant capacity (TAC), malondialdehyde (MDA), and specific activity of hepatic catalase were measured. BAT UCP1 expression was evaluated at both the mRNA and protein levels. RESULTS The weights differed between the groups (p<0.05). Serum MDA was greater and TAC, liver catalase, and PON1 were less than in group 2 than in group 1 (p<0.05). In Serum MDA was less and catalase activity was greater in group 3 than in group 2 (p<0.05). UCP1 gene expression was less in group 2 than in group 1 (p<0.05) but greater than in group 3 (p<0.05). CONCLUSIONS Pioglitazone may have a protective role in high-fat-diet-induced oxidative stress by increasing the antioxidant capacity. Moreover, it can induce weight loss by increasing UCP1 mRNA and protein expression.