Obesity has recently been defined as a chronic inflammatory disease and is considered as a major cause of adult health problems including incurable diseases like diabetes and cancer. In this study, the systemic immunity, including the innate and adaptive immunity parameters, of naturally occurring (leptin receptor mutation) obesity-diabetes mice (db/db) was examined to increase our knowledge of these mice for obesity-related studies. Severe fatty liver with blood engorgement was observed in the db/db mice. Compared to background C57BL/6J mice, the adaptive immunity, as measured by mitogen-induced T and B cell proliferation and cytokine release, was significantly suppressed in db/db mice. However, significant upregulation of innate immune-inflammatory parameters including macrophage function and NK cell activity was observed in db/db mice without external stimulation. These data conclusively confirm the systemic immune-inflammatory micro-environment with suppressed adaptive immunity of db/db mice, which may cause the secondary obesity-related life-threatening diseases like diabetes or cancer.