Objective: Pioglitazone has been known for its anti-atherogenic effects. We compared the effects of pioglitazone in reducing atherosclerosis progression and neointima volume in type 2 diabetic patients. Methods: This was a prospective, randomized single-blinded, 8-month follow-up study, and type 2 diabetic patients with significant coronary artery stenosis were randomly assigned to either pioglitazone (n=19) or placebo (n=18) after zotarolimus-eluting stent (ZES) implantation. Intravascular ultrasonography (IVUS) at culprit vessel was performed from 20mm distal and proximal to the stent at baseline and at 8-month, and volumetric analysis was performed. Changes in inflammation markers, insulin resistance and lipid profile were compared. Results: Changes in atherosclerosis progression from baseline in the Pioglitazone Group was significantly lower than that of the Placebo Group. (0.06 짹 0.73 vs. 1.16 짹 1.41 mm3/mm, p=0.024, respectively), and neointima volume was significantly lower in the Pioglitazone Group compared with the Placebo Group (1.74 짹 0.93 vs. 2.42 짹 1.98, p=0.007, respectively). HOMA-index, Interleukin (IL)-6, and tumor necrosis factor (TNF)-慣 levels were significantly lower at 8 months in the Pioglitazone Group when compared to the Placebo Group. RBP-4 levels revealed no significant differences between the 2 groups during the 8-month follow-up. Major adverse cardiovascular events (MACEs) were similar between the 2 groups. Conclusions: Pioglitazone, when compared with placebo, was associated with a significant reduction in atherosclerosis progression and neointima formation in type 2 diabetic patients with ZES implantation.