Acute highintensity interval exercise reduces human monocyte Toll-like receptor 2 expression in type 2 diabetes. Am J Physiol Regul Integr Comp Physiol 312: R529 -R538, 2017. First published January 25, 2017; doi:10.1152/ajpregu.00348.2016.-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. The purpose of this study was to determine the impact of a single session of HIIT on cellular, molecular, and circulating markers of inflammation in individuals with T2D. Participants with T2D (n 10) and healthy age-matched controls (HC; n 9) completed an acute bout of HIIT (7 1 min at ~85% maximal aerobic power output, separated by 1 min of recovery) on a cycle ergometer with blood samples obtained before (Pre), immediately after (Post), and at 1 h of recovery (1-h Post). Inflammatory markers on leukocytes were measured by flow cytometry, and TNF- was assessed in both LPS-stimulated whole blood cultures and plasma. A single session of HIIT had an overall anti-inflammatory effect, as evidenced by 1) 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); 2) significantly lower LPSstimulated TNF- release in whole blood cultures at 1-h Post (P 0.05 vs. Pre); and 3) significantly lower levels of plasma TNF- 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- in HC vs. T2D (group time interaction, P 0.05). One session of low-volume HIIT has immunomodulatory effects and provides potential antiinflammatory benefits to people with, and without, T2D.