Background: Adipocytokines are important in type 2 diabetes (T2D). This study explored adipocytokine associations with acute and chronic hyperglycemia in African American Men (AAM). Methods: Fourteen adipocytokines were measured (multiplex assay) in blood samples from men with normal glucose tolerance (NGT) or T2D (drug-naïve MF(-) or using metformin MF(+)). Acute and chronic hyperglycemia were evaluated at 120-minute of OGTT and by HbA1c, respectively. Results: AAM with T2D (N=21) compared to NGT (N=20) were significantly older (59 vs. 54 years) and had higher body mass index (BMI 35 vs. 27 kg/m2) (p<0.01 for both). Fasting and 120-minute OGTT glucose and insulin were higher in T2D than NGT, however, differences did not reach statistical significance after adjusting for age and BMI. In the fasted state, TNF-a, IL-6, PAI-1 (p<0.01 for all) and IL-13, adiponectin, adipsin, lipocalin (p<0.05 for all) were lower in T2D compared to NGT. At 120-minute post-glucose load (acute hyperglycemia) TNF-a, IL-6, IL-13, IL-8, PAI-1, adiponectin, adipsin (p<0.01 for all) and lipocalin, resistin (p<0.05 for both) were lower in T2D than in NGT group. There were no statistical differences for the other adipocytokines including GM-CSF, IL-7, IL-10, IP-10, and MCP-1. Regression analysis (adjusted for age and BMI) showed that fasting IL-8, TNF-a, adiponectin, lipocalin, resistin, adipsin, and PAI-1 were all associated with HbA1c (p<0.05 for all). Further modeling revealed that after adjusting for age, BMI, glucose tolerance status and metformin use, only adipsin remained significantly associated with HbA1c (p=0.004). The model including adipsin, TNF-a, age, BMI, and group designation (i.e. NGT, MF(-), MF(+)) explained 86% of HbA1c variability. Conclusions: The study suggested that adipsin could be independently associated with HbA1c in AAM with varied glucose tolerance. Additional studies should corroborate these data and provide mechanistic insights for enabling adipsin-related discoveries of novel T2D treatment.