FGF-21 has been recently characterized as a potent metabolic regulator, but its pathophysiologic role in human remains unknown. In this study we investigate whether plasma FGF-21 level is different in patients with new-onset type 2 diabetes mellitus (T2DM) and diabetic ketosis (T2DK). Sixty-eight patients with T2DM, 41 subjects with T2DK, and 52 sex- and age-matched normal controls participated in the study. Plasma FGF-21 levels were measured with a radioimmunoassay. The relationship between plasma FGF-21 levels and anthropometric and metabolic parameters was also analyzed. Plasma FGF-21 levels were higher in patients with T2DK and T2DM than in controls (4.05+/-0.18microg/L and 2.82+/-0.14microg/L vs. 2.28+/-0.16microg/L, P<0.01 and P<0.05, respectively). Fasting plasma FGF-21 was found to correlate positively and significantly with SBP, DBP, FBG, 2hPBG, HbA(1)c, HDL-C and FFA, but negatively with fasting plasma insulin, 2hIns and HOMA(IS). Multiple regression analysis showed that DBP, WHR, 2hIns, 2hPBG and FFA were independent to the factors influencing plasma FGF-21 levels. Increasing concentrations of FGF-21 were independently and significantly associated with T2DM and T2DK. The present work suggests that FGF-21 may play a role in the pathogenesis of T2DM and T2DK.