Adiponectin, which is produced by adipose tissue, is thought to play an important role in inflammation. On the other hand, adiposity, or the hypertrophy of adipose tissue, has been reported to increase oxidative stress. Accordingly, the possibility exists that adiponectin, as well as leptin, influences oxidative stress, resulting in a proinflammatory state. However, the relationship between adiponectin and oxidative stress is unclear. We examined 259 Japanese Americans living in Hawaii who were diagnosed as having normal glucose tolerance (NGT), impaired glucose tolerance, or diabetes by a 75-g oral glucose tolerance test. First, we measured their serum adiponectin, leptin, and high-sensitivity C-reactive protein levels as markers of inflammation, and urinary 8-iso-protaglandin F(2 alpha) (isoprostane) as a relevant marker of oxidative stress. We investigated the relationship between adiponectin or leptin and isoprostane among these subjects. In the diabetic subjects, the adiponectin and leptin levels were significantly lower and higher, respectively, than among the NGT subjects. Urinary isoprostane levels tended to decrease significantly after a rise in adiponectin levels (P = .014) among the NGT subjects. Next, we investigated the association between the 2 adipocytokines and isoprostane by regression models. Adiponectin was negatively but significantly associated with urinary isoprostane levels adjusted for age, gender, and smoking status, whereas leptin was positively and significantly correlated with urinary isoprostane levels (P = .014 and .004, respectively). With respect to adiponectin, this association was attenuated but still significant when further adjustments were made for waist-to-hip ratio, body mass index, percent body fat, C-reactive protein levels, glucose tolerance status, or homeostasis model assessment. In conclusion, this study suggests that adiponectin and leptin might be associated with oxidative stress levels. These results also suggest the possibility that adiponectin might modulate oxidative stress, leading to antidiabetic and anti-arteriosclerotic effects.