OBJECTIVE To test whether differences in serum concentrations of adiposity-related low-grade inflammatory mediators could help to differentiate patients with latent autoimmune diabetes in adults (LADA), classic adult-onset type 1 diabetes, and type 2 diabetes. RESEARCH DESIGN AND METHODS This cross-sectional study involved 75 patients with LADA, 67 with classic adult-onset type 1 diabetes, and 390 with type 2 diabetes. Serum concentrations of adiponectin, soluble tumor necrosis factor-α receptor 2 (sTNFRII), interleukin-6, hs-CRP, and total leukocyte number were measured. To evaluate the differences of these markers among diabetes types, we performed logistic regression models and evaluated area under the receiver-operating characteristic curve (AUCROC) values. RESULTS The profile of innate immunity-related inflammatory markers correlated with metabolic syndrome components. LADA versus classic adult-onset type 1 diabetes was independently related to sTNFRII (odds ratio [OR] 1.9 [95% CI 1.01–3.97]; P = 0.047) and hs-CRP levels (OR 0.78 [95% CI 0.62–0.96]; P = 0.019), and a higher number of total leukocytes lowered the risk of LADA compared with type 2 diabetes (OR 0.98 [95% CI 0.97–0.99]; P = 0.036). The logistic regression model including explanatory biomarkers explained 35% of the variation for LADA versus classic adult-onset type 1 diabetes (AUCROC 0.83 [95% CI 0.74–0.92]; P < 0.001) and 15% of the variation for LADA versus type 2 diabetes (AUCROC 0.73 [95% CI 0.70–0.80]; P < 0.001). CONCLUSIONS Inflammatory, adiposity, and immune-related markers could help to differentiate a LADA diagnosis from that of classic adult-onset type 1 diabetes, and also LADA from that of type 2 diabetes, along with islet autoantibody positivity.