We examined male and female glucose transporter isoform 3 (GLUT3; placenta) null heterozygous^+/- mutation carrying mice and compared them to age- and sex-matched wild type^+/+ littermates. No difference in postnatal (1-2d, 6-7d, 12-13d, 20-21d), post-suckling (1-2 months) and adult (3-6 months) growth pattern was seen except for an increase in body weight of 9-11 month old male but not female GLUT3^+/- mice. This change in male mutant mice was associated with increased total body fat mass, peri-renal and epididymal white adipose tissue weight and hepatic lipid infiltration. These minimally glucose intolerant male mutant mice demonstrated no change in caloric intake but a decline in basal metabolic rate and insulin resistance. No perturbation in basal circulating glucose concentrations but an increase in insulin concentrations, triglycerides and total cholesterol was observed in GLUT3^+/- male mice. Tissue analysis in males and females demonstrated diminished GLUT3 protein in GLUT3^+/- brain and skeletal muscle with no change in brain and adipose tissue GLUT1 protein concentrations. Further the male GLUT3^+/- mice expressed decreased insulin responsive GLUT4 in white adipose tissue and skeletal muscle sarcolemma. We conclude that the GLUT3^+/- male mice develop adult-onset adiposity with insulin resistance.