Obesity and insulin resistance are common features of Type 2 Diabetes. A new protein called resistin has been shown to be secreted by adipocytes in mice and to influence insulin sensitivity. The goal of the present study was to investigate the associations between one polymorphism (g-420C>G) of the human resistin gene and phenotypes related to adiposity and glucose metabolism. We genotyped 725 (including 42 diabetics) adult subjects participating in the Quebec Family Study (QFS) by a minisequencing method. Forty-two were diabetic subjects. Phenotypes measured were: body mass index (BMI) and waist circumference (WC), % body fat (PFAT) and fat mass (FM) assessed by under water weighing, abdominal total, subcutaneous and visceral fat assessed by computed tomography and fasting plasma glucose, insulin and C-peptide and their responses to an oral glucose tolerance test (OGTT). Comparisons between genotypes were performed in non-diabetic men (no.=280) and women (no.=403) separately by analyses of covariance (ANCOVA). Among men, g-420 G homozygotes had less visceral fat (p < 0.05), lower levels of acute insulin responses to an OGTT and lower levels of C-peptide in a fasting state and in responses to an OGTT than carriers of the C allele (p < 0.01). These associations were independent of age and adiposity but were not observed in women. These results suggest that in men, the human resistin gene is associated with reduced amount of visceral obesity and lower insulin secretory responses to a glucose load.