Type 2 diabetes (T2D) is characterized by chronic low-grade inflammation that contributes to disease pathophysiology. Exercise has anti-inflammatory effects but the impact of high-intensity interval training (HIIT) is not known. PURPOSE: To determine the impact of a single session of HIIT on cellular, molecular, and circulating markers of inflammation in individuals with T2D. METHODS: Participants with T2D (n=10) and healthy age-matched controls (HC; n=9) completed an acute bout of HIIT (7 X 1-min @ ~85% maximal aerobic power output, separated by 1-min recovery) on a cycle ergometer with blood samples obtained before (Pre), immediately after (Post), and at one-hour of recovery (1-h Post). Inflammatory markers on leukocytes were measured by flow cytometry, and tumor necrosis factor (TNF)-α assessed in both lipopolysaccharide (LPS)-stimulated whole blood cultures and plasma. RESULTS: A single session of HIIT had an overall anti-inflammatory effect, as evidenced by: i) significantly lower levels of toll-like receptor (TLR) 2 surface protein expression on both classical and CD16+ monocytes assessed at Post and 1-h Post compared with Pre (p<0.05 for all); ii) significantly lower LPS-stimulated TNF-α release in whole blood cultures at 1-h Post (p<0.05 vs. Pre); and iii) significantly lower levels of plasma TNF-α at 1-h Post (p<0.05 vs. Pre). There were no differences between T2D and HC except for a larger decrease in plasma TNF-α in HC vs. T2D (group x time interaction, p<0.05). CONCLUSIONS: One session of low-volume HIIT has immunomodulatory effects and provides potential anti-inflammatory benefits to people with, and without, T2D.