Thiazolidinediones (TZD) may improve insulin resistance in patients with diabetes and HIV. The novel adipocytokines visfatin and retinol-binding protein-4 (RBP-4) have been proposed to influence the development of impaired glucose tolerance. The impact of TZD on these cytokines is yet unknown. In this randomized, double-blind, placebo-controlled parallel group study, 37 lean HIV-positive subjects aged 19-50 years were treated with 8 mg/day rosiglitazone (n=20) or placebo (n=17) for 6 months. Insulin sensitivity was estimated from the homeostasis model assessment (HOMA) index. Fasting visfatin, RBP-4, leptin, and adiponectin plasma concentrations were analyzed by immunoassays. Rosiglitazone had no effect on impaired insulin sensitivity, but increased median plasma visfatin from 6.2 ng/ml (95% CI: 5.9; 6.5) to 13.7 ng/ml (12.6; 19.1) (P<0.001) and adiponectin from 3.2 ng/ml (2.2; 4.0) to 4.0 ng/ml (3.3; 8.5; P<0.001). RBP-4 was lowered from 21.0 ng/ml (19.6; 23.1) to 16.3 ng/ml (15.2; 17.0; P<0.001), and leptin concentrations were unchanged. Adipocytokine concentrations were stable in subjects receiving placebo, where a deterioration in insulin sensitivity was detectable (P<0.05). Changes in visfatin and RBP-4 were correlated in subjects receiving rosiglitazone (r=-0.64, P<0.01) but not placebo (r=0.12, P=0.15). TZD treatment affects circulating adipocytokine concentrations in subjects with HIV. Reductions in RBP-4 and increases in visfatin may contribute to the pharmacodynamic action of TZD on glucose homeostasis. Quantification of adipocytokines might be useful to assess TZD treatment effectiveness in insulin-resistant subjects with HIV.