We describe a line of transgenic rats in which the males develop a unique autosomal dominant Late-onset OBesity (LOB) phenotype. LOB males gradually accumulate fat specifically in visceral but not peripheral fat depots despite a normal intake of a low fat diet. LOB females normally develop only mild obesity with advanced age. However, the phenotype can be induced rapidly in young females by ovariectomy and prevented by estrogen replacement. LOB males are highly sensitive to dietary fat. Young, non-obese LOB males gain more weight on a 30% fat diet, and lose more weight when treated with the lipase inhibitor, Orlistat, than their non-transgenic littermates. Remarkably, despite severe visceral obesity, LOB rats have normal fasting blood glucose, insulin and corticosterone, show normal or increased insulin sensitivity in glucose-, and insulin- tolerance tests, increased plasma adiponectin levels and an heightened response to treatment with rosiglitazone. Their visceral adiposity reflects specific increase in visceral adipocyte number, not size. Analysis of the transgene in LOB rats revealed a deletion in the gene encoding the S26 subunit of the mitochondrial ribosome that results in production of a truncated protein, which we show to be imported into mitochondria. However, the transgene integrant is complex, so whether this is the sole molecular disruption underlying this phenotype remains to be established. Nevertheless, LOB rats provide a valuable new model of late-onset, male-preponderant, visceral-specific obesity, clearly dissociated from insulin resistance.