Background. Adiponectin, an anti-inflammatory and insulin-sensitizing cytokine, has been shown to reduce proteinuria and glomerulosclerosis in experimental models. We assessed the relationship of plasma adiponectin to the progression of kidney disease in type 2 diabetes (T2D) patients. Methods. T2D nonnephrotic patients with glomerular filtration rate (GFR) > 30 ml/min and without acute cardiovascular/inflammatory conditions were included. Laboratory standard evaluation, urinary albumin/creatinine ratio (UACR), total plasma adiponectin, and CRP (C-reactive protein) were determined at inclusion and the end of study. Results. Eighty-six patients (62.79% male) were followed up for 20.53 +/- 5.46 months. Baseline GFR was 72.85 +/- 26.29 ml/min and UACR was 20.53 (interquartile range 6.82-86.39) mg/g. At baseline adiponectin was significantly correlated to UACR (r = 0.40, p = 0.0001), HDL cholesterol (r = 0.30, p = 0.005), GFR (r = -0.23, P = 0.04), body mass index (BMI) (r = -0.26, P = 0.02) and waist circumference (r = -0.27, p = 0.01). In multiple regression UACR (p = 0.0003) and BMI (p = 0.03) were significantly related to baseline adiponectin. The progression of kidney disease was estimated as the difference (Delta) between end and baseline UACR/month and between end and baseline GFR/month. None of the baseline parameters correlated to Delta GFR, but adiponectin inversely (r = -0.26, p = 0.02) correlated to D UACR. In multiple regression only adiponectin (p < 0.0001) predicted Delta UACR. A computed progression index (PI) resulting from a linear combination of GFR and UACR was also used to assess progression. Baseline adiponectin was significantly correlated to Delta PI between end of study and baseline (r = -0.43, p < 0.0001), and predicted Delta PI in multiple regression (p = 0.009). Conclusion. Low plasma adiponectin predicts progression of kidney disease in T2D patients.