OBJECTIVE:: To explore the association of promoter polymorphisms of macrophage migration inhibitory factor (MIF) gene with obesity. SUBJECTS:: In total, 213 nondiabetic Japanese subjects. They were divided into three groups according to World Health Organization definitions: lean (bodymass index (BMI)<25 kg/m), overweight (25≤BMI<30 kg/m) and obese (BMI≥30 kg/m). METHODS:: We examined two polymorphic loci in the MIF gene in the subjects: a single-nucleotide polymorphism at position −173 (G/C) and a CATT-tetranucleotide repeat polymorphism at position −794, which both can affect promoter activity in different cells. RESULTS:: We detected four alleles: 5-, 6-, 7- and 8-CATT at position −794. Genotypes without the 5-CATT allele (X/X, X refers to 6-, 7- or 8-CATT alleles) were more common in obese subjects than in lean or overweight groups (P=0.013). The X-CATT allele was more frequent in obese subjects than in lean or overweight subjects (P=0.030). In contrast, −173G/C was not associated with obesity. Among the haplotypes of the two promoter polymorphisms, G/5-CATT ((−173G/C)/(−794[CATT]5-8)) was associated with a decreased risk of obesity (P=0.025) and G/6-CATT with an increased risk of overweight (P=0.028). CONCLUSION:: Promoter polymorphism in the MIF gene is linked with obesity.