Background: Dyslipidemia, dysregulated adipokine secretion and alteration in glucagon and adropin concentrations are important obesity-related factors in the pathophysiology of human Type 2 diabetes; however, their roles in the pathophysiology of feline diabetes mellitus are relatively unknown. Here, we determined the concentrations of circulating leptin, adiponectin, pro-inflammatory cytokines, glucagon, adropin, triglycerides, and cholesterol, in non-diabetic lean and overweight cats and newly diagnosed diabetic cats. Client-owned cats were recruited and assigned into 3 study groups: lean, overweight and diabetic. Fasting blood samples were analyzed in lean, overweight and diabetic cats at baseline and 4 weeks after consumption of high protein/low carbohydrate standardized diet. Results: Serum concentrations of triglycerides were greater in diabetics at baseline and were increased in both diabetic and overweight cats at 4 weeks. Plasma leptin concentrations were greater in diabetic and overweight at baseline and 4 weeks, whereas adiponectin was lower in diabetics compared to lean and overweight cats at baseline and 4 weeks. Diabetics had greater baseline plasma glucagon concentrations compared to lean, lower adropin than overweight at 4 weeks, and lower IL-12 concentrations at 4 weeks than baseline. Conclusions: Our results suggest that feline obesity and diabetes mellitus are characterized by hypertriglyceridemia and hyperleptinemia; however, diabetic cats have significantly lower adiponectin and adropin compared to overweight cats. Thus, despite having similar body condition, overweight and diabetic cats have differential circulating concentrations of adiponectin and adropin.