Obese subjects usually have hyperaminoacidemia. Metabolomics studies also indicate the elevation of plasma branched-chain (BCAA) and aromatic (AAA) amino acids can be used to assess the development of obesity-related type 2 diabetes mellitus. Although an altered plasma amino acid profile in male genetically obese (ob/ob) mice at 13 wks of age has been reported, the profile at pre-obese period or between sexes has yet been elucidated. The compositions of plasma amino acids in the ob/ob mice with both sexes at 4 and 8 wks of age (WOA) were assessed by the method of high performance liquid chromatography. The ob/ob mice (male at both ages, 8-WOA female) had significant elevation in plasma large neutral amino acids (LNAA=BCAA+AAA) than their lean controls. In addition, LNAA value was significantly correlated with food intake (r=0.64) and body weight (r=0.57). Besides LNAA, ob/ob mice also had sex- and age-related reduction in glutamine (4- WOA male, female at both ages) and glycine (male at both ages), and elevation in ornithine (8-WOA male, 8-WOA female) and taurine (male at both ages, 8-WOA female). Our data indicated the ob/ob mice, even before at pre-obese period, exhibited diabetic-prone pattern of p