BACKGROUND Insulin resistance, a strong risk factor for atherosclerotic vascular disease, is present in uremic patients without diabetes on continuous ambulatory peritoneal dialysis (CAPD) therapy. Amelioration of insulin resistance may reduce associated long-term cardiovascular complications. The aim of the study is to investigate the effects of rosiglitazone (ROS), an insulin sensitizer, on glucose metabolism in CAPD patients without diabetes. METHODS Fifteen uremic patients without diabetes on CAPD therapy were enrolled. All were administered ROS, 4 mg/d, for 12 weeks. A control group consisted of 15 age- and sex-matched healthy subjects. Oral glucose tolerance test (OGTT) results, fasting glucose and insulin levels, related blood biochemistry results, and C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels were determined before initiation and at 4 and 12 weeks of therapy. Insulin resistance was evaluated using the homeostasis model assessment method (HOMA-IR). A whole-body insulin sensitivity index (ISI) and insulinogenic index for insulin production were calculated from OGTT results. RESULTS CAPD patients showed significantly greater HOMA-IR and glucose intolerance compared with healthy controls. After 4 and 12 weeks of ROS therapy, there were no significant changes in body weight, blood pressure, dialysis adequacy, hemoglobin level, hemoglobin A(1c) level, liver function, lipid profile, or intact parathyroid hormone, CRP, IL-6, or TNF-alpha levels. There was a significant decrease in HOMA-IR (3.2 +/- 0.6, 2.2 +/- 0.4, and 2.1 +/- 0.4; P < 0.05). During the OGTT, there was a significant decrease in the area under the glucose curve and a significant increase in ISI (3.5 +/- 0.4, 5.0 +/- 0.7, and 5.3 +/- 0.7; P < 0.05), but no significant change in insulinogenic index. CONCLUSION ROS improved insulin resistance in CAPD patients without diabetes. Whether long-term use of ROS reduces cardiovascular risk needs further study.