Objective: The objective was to investigate associations of regional fat depots with adipokines, inflammatory markers, and risk of metabolic syndrome (MetS) in a Chinese population. Design and Methods: Trunk and leg fat mass were determined in a population-based sample of 1150 Chinese (479 men and 671 women) aged 50-70 yr by using whole-body dual-energy x-ray absorptiometry scan. Plasma adiponectin, plasminogen activator inhibitor-1 (PAI-1), retinol-binding protein 4 (RBP4), resistin, C-reactive protein, and IL-6 were measured. The updated National Cholesterol Education Program Adult Treatment Panel III criterion for Asian Americans was used to define MetS. Results: Larger body-size adjusted trunk fat mass was significantly associated with lower adiponectin and higher PAI-1, RBP4, C-reactive protein, and IL-6 levels in both genders (P < 0.05). Larger body-size adjusted leg fat mass was significantly associated with higher adiponectin levels in both genders but lower RBP4 and PAI-1 concentrations in men (P < 0.05). Comparing with the lowest body-size adjusted leg fat mass tertile, the odds ratio (95% confidence interval) of MetS in the highest tertile was 0.33 (0.18-0.62; P for trend <0.001) for men and 0.43 (0.28-0.65; P for trend <0.001) for women. The association was attenuated with further controlling adipokines and inflammatory markers (P = 0.09 for men and P = 0.004 for women). Conclusion: In contrast to trunk fat, large leg fat appears to have favorable effects on adipokines, inflammatory markers, and MetS risk among Chinese. The opposite associations between regional fat depots and MetS risk may partially mediated by adipokines and inflammatory status. Copyright © 2010 by The Endocrine Society