BACKGROUND: This study aimed to evaluate the effect of pioglitazone as an insulin sensitizer on circulating interleukin-10 (IL-10) as an anti-inflammatory factor and tumor necrosis factor-alpha (TNF-α) as main proinflammatory factor in non-diabetic metabolic syndrome (MetS) patients in Caucasians race of Middle East area in Iran. METHODS: We conducted a randomized double-blind controlled study of 68 non-diabetic patients with MetS. Patients were randomly divided into two groups including intervention group received pioglitazone 30 mg daily for 24 weeks, and the control group received placebo pills for the same duration. Circulating levels of TNF-α and IL-10 were assessed as a primary goal. Lipid profile, liver enzymes, blood pressure (BP), waist circumference, and body mass index (BMI) also were measured. RESULTS: Lipid profile and fasting blood sugar had non-significant changes after treatment by pioglitazone, but BMI was increased significantly (P = 0.002). BP and waist circumference had a significant decrease in both groups (P < 0.050). Aspartate transaminase and alanine transaminase were decreased significantly in the pioglitazone group (P = 0.002). TNF-α decreased non-significantly in both groups (P > 0.050). IL-10 increased in intervention group non-significantly (P = 0.971); whereas in placebo group decreased to a little extent (P = 0.401). C-reactive protein was also decreased insignificant after receive pioglitazone (P = 0.333). There was no significant difference in all variables between the two groups (P > 0.050) except liver enzymes (P < 0.050). CONCLUSION: This study indicates that the pioglitazone has no positive effect on improving inflammatory status in the non-diabetes patients with MetS.