The A^y allele at the agouti locus causes obesity and promotes linear growth in mice. However, body weight gain stops between 16 and 17 weeks after birth, and then, body weight decreases gradually in DDD.Cg-A^y male mice. Body weight loss is a consequence of diabetes mellitus, which is genetically controlled mainly by a quantitative trait locus (QTL) on chromosome 4. This study aimed to further characterize diabetes mellitus and body weight loss in DDD.Cg-A^y males. The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-A^y males. Using a backcross progeny of DDD × (B6 × DDD.Cg-A^y) F₁-A^y, we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight. The DDD allele was associated with decreased plasma insulin levels. When the DDD.Cg-A^y males were housed under three different housing conditions [group housing (4 or 5 DDD.Cg-A^y and DDD males), individual housing (single DDD.Cg-A^y male) and single male housing with females (single DDD.Cg-A^y male with DDD.Cg-A^y or DDD females)], diabetes mellitus and body weight loss were most severely expressed in individually housed mice. Thus, the severity of diabetes and body weight loss in the DDD.Cg-A^y males was strongly influenced by the housing conditions. These results demonstrate that both genetic and nongenetic environmental factors are involved in the development of diabetes mellitus and body weight loss in the DDD.Cg-A^y males.