In this study, the regional adipose tissue-adiponectin (AT-ADN) and adiponectin receptor (R1 and R2) expression and their relation with metabolic parameters, circulating and AT-derived cytokine expressions were compared. Paired subcutaneous adipose tissue (SCAT) and visceral adipose tissue (VAT) were taken from 18 lean and 39 obese humans, AT-mRNA expression of adipokines analysed by RT-PCR and corresponding serum levels by enzyme-linked immunosorbent assay (ELISA). R1 and R2 adipocyte expression was compared with 17 other human tissues. ADN-gene expression was lower in VAT than SCAT [mean (SD) 1.54 (1.1) vs. 2.84 (0.87); p < 0.001], and lower in obese subjects (VAT : p = 0.01;SCAT : p < 0.001). SCAT-ADN correlated positively with serum ADN (r = 0.33;p = 0.036) but not VAT-ADN. AT expressions of ADN and macrophage migration inhibiting factor (MMIF), IL18 and cluster of differentiation factor 14 (CD14) in both depots showed inverse correlations. R1 and R2 were expressed ubiquitously and R2 highest in SCAT, and this is much higher (x100) than R1 (x100). R expression was similar in lean and obese subjects and unrelated to the metabolic syndrome, however, receptors correlated with VAT-MMIF (R 1: r = 0.4;p = 0.008;R 2: r = 0.35,p = 0.02) and SCAT-MMIF expression (R 2: r = 0.43;p = 0.004). Unlike ADN, its receptors are expressed in many human tissues. Human R2 expression is not highest in the liver but in AT where it is associated with MMIF expression. The adiponectin-dependent insulin-sensitizing action of thiazolidinediones is thus probably to differ amongst species with weaker effects on the human liver.