Obesity increases with aging. Methionine restriction affects lipid metabolism and can prevent obesity in mice. In the present study we observed C57BL/6 mice to double their body weight from 4 to 48 weeks of age and become obese. We evaluated the efficacy of oral administration of recombinant-methioninase (rMETase)-producingE. coli(E. coliJM109-rMETase) or a methionine-deficient diet to reverse old-age-induced obesity in C57BL/6 mice. Fifteen C57BL/6 male mice aged 12–18 months with old-age-induced obesity were divided into three groups. Group 1 was given a normal diet supplemented with non-recombinantE. coliJM109 cells orally by gavage twice daily; Group 2 was given a normal diet supplemented with recombinantE. coliJM109-rMETase cells by gavage twice daily; and Group 3 was given a methionine-deficient diet without treatment. The administration ofE. coliJM109-rMETase or a methionine-deficient diet reduced the blood methionine level and reversed old-age-induced obesity with significant weight loss by 14 days. There was a negative correlation between methionine levels and negative body weight change. Although the degree of efficacy was higher in the methionine-deficient diet group than in theE. coliJM109-rMETase group, the present findings suggested that oral administration ofE. coliJM109-rMETase, as well as a methionine-deficient diet, are effective in reversing old-age-induced obesity. In conclusion, the present study provides evidence that restricting methionine by either a low-methionine diet orE. coliJM109-rMETase has clinical potential to treat old-age-induced obesity.