Abstract We investigated the relationship between Ala54Thr variant allele of the fatty acid-binding protein 2 (FABP2) gene (Ala54Thr) and development of obesity in Japanese obese women. FABP2 genotypes were determined with a fluorescent allele-specific DNA primer assay system. Body weight, waist and hip circumference, amounts of visceral and subcutaneous white adipose tissue measured by computed tomography (CT) were compared between subjects with Thr allele and without Thr allele before and after the diet and exercise therapy in 80 Japanese obese women. The frequency of the Thr54 allele did not differ between obese and control subjects (0.388 versus 0.329, respectively). In subjects with Ala/Thr and Thr/Thr genotype, adjusted resting metabolic rate (RMR) was significantly lower than the subjects with Ala/Ala genotype. Subjects with the Thr54 allele showed significantly greater waist circumference after diet and exercise therapy than subjects with Ala/Ala genotype. They also demonstrated greater body weight at 20 years of age compared to subjects with Ala/Ala genotype. In conclusion, Thr54 allele of FABP2 has associations with lower adjusted resting metabolic rate, resistance in reducing visceral white adipose tissue (WAT) and early onset of obesity in Japanese obese women.