Obesity-related insulin resistance is associated with changes in adipose tissue release of leptin, adiponectin, and nonesterified fatty acids (NEFAs). We have previously described that persons originating from the Indian subcontinent (Asian Indians) manifest excessive insulin resistance even in the absence of obesity. Therefore, in this study, we tested the hypothesis that nondiabetic, insulin-resistant Asian Indians differ from less insulin-resistant Caucasians of similar age and body composition in adipose tissue production of leptin and adiponectin, and in suppression of plasma NEFA concentrations during hyperinsulinemia. Seventy-nine Asian Indian men were compared with 61 Caucasian men. Higher plasma NEFAs and leptin in Asian Indians (P < 0.0001 and P = 0.003 for NEFAs and leptin, respectively) and lower plasma concentrations of adiponectin (P = 0.009) were not explained by body fat content and distribution. Oral glucose tolerance test studies revealed that Caucasian men had greater suppression of plasma NEFAs than Asian Indian men. We conclude that plasma concentrations of the adipose tissue metabolites leptin and NEFAs are higher and that of adiponectin is lower in insulin-resistant Asian Indians compared with more insulin-sensitive Caucasians. These differences may contribute to the excessive prevalence of type 2 diabetes and cardiovascular disease in nonobese Asian Indians.