It is generally recognized that obesity and cardiometabolic risk are more prevalent in African Americans. Kallistatin, a novel tissue kallikrein inhibitor, has anti-inflammatory and anti-oxidant properties. Thus, the goal of this study was to examine the relationships among plasma kallistatin levels, adiposity and cardiometabolic risk factors in African American adolescents.Plasma kallistatin levels were determined in 318 apparently healthy African American adolescents (aged 14-19 years, 48.1% females) by enzyme-linked immunosorbent assay.Plasma kallistatin levels did not differ between males (27.9±11.2 μg/mL) and females (26.8±11.0 μg/mL) (p=0.47). Plasma kallistatin levels were inversely correlated with percent body fat (% BF, r=-0.13, p=0.04), total cholesterol (r=-0.28, p<0.01), low density lipoprotein cholesterol (LDL, r=-0.30, p<0.01) and interleukin-6 (r=-0.14, p=0.05), but positively correlated with adiponectin (r=0.16, p=0.03) and high density lipoprotein (HDL, r=0.17, p=0.02). These correlations remained significant after adjustment for age, sex and body mass index percentiles. Stepwise multiple linear regression analysis showed that LDL cholesterol alone explained 14.2% of the variance in kallistatin, while % BF and adiponectin explained an additional 3.6% and 2.8% of the variance, respectively.The present study demonstrates that plasma kallistatin levels are inversely associated with adiposity, adverse lipid profiles and inflammation in apparently healthy African American adolescents. As a potent antioxidant and anti-inflammation agent, kallistatin may also hold therapeutic promise in cardiometabolic disorders.