There have been increasing evidences that thiazolidinediones, peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, may have some antiatherogenic actions. We have previously reported that troglitazone has a potent inhibitory effect on common carotid arterial intima-media thickness (IMT) in subjects with type 2 diabetes. However, some studies suggested a possibility that PPARgamma activators may have protoatherogenic actions, raising concern about their detrimental effects in diabetic subjects. In the present study, we investigated the effect of treatment with pioglitazone, another PPARgamma agonist, on IMT in a total of 106 Japanese subjects with type 2 diabetes. Pioglitazone (30 mg daily) was administered for 6 months in 53 patients. Compared to control group (n = 53), the group given pioglitazone showed a significant decrease in IMT as early as 3 months after the administration. The decrease in IMT was also found after 6 months (IMT change: -0.084[SE 0.023] mm vs. control 0.022[SE 0.006] mm, P < 0.001), although the difference between those after 3 and 6 months did not reach any statistical significance. These findings indicate that thiazolidinediones cause an inhibition of early atherosclerotic process PPARgamma activation.