Epidemiologic evidence suggests that serum carotenoids are potent antioxidants and may play a protective role in the development of chronic diseases including cancers, cardiovascular disease, and inflammatory diseases. The role of these antioxidants in the pathogenesis of diabetes mellitus remains unclear.This study examined data from a cross-sectional survey to investigate the association between serum carotenoids and type 2 diabetes.Study participants were adults aged > or = 25 y (n = 1597) from 6 randomly selected cities and towns in Queensland, Australia. Study examinations conducted between October and December 2000 included fasting plasma glucose, an oral-glucose-tolerance test, and measurement of the serum concentrations of 5 carotenoid compounds.Mean 2-h postload plasma glucose and fasting insulin concentrations decreased significantly with increasing quintiles of the 5 serum carotenoids--alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, and lycopene. Geometric mean concentrations for all serum carotenoids decreased (all decreases were significant except that of lycopene) with declining glucose tolerance status. Beta-carotene had the greatest decrease, to geometric means of 0.59, 0.50, and 0.42 micromol/L in persons with normal glucose tolerance, impaired glucose metabolism, and type 2 diabetes, respectively (P < 0.01 for linear trend), after control for potential confounders.Serum carotenoids are inversely associated with type 2 diabetes and impaired glucose metabolism. Randomized trials of diets high in carotenoid-rich vegetables and fruit are needed to confirm these results and those from other observational studies. Such evidence would have very important implications for the prevention of diabetes.