High-intensity exercise suppresses appetite partly through changes in peripheral appetite-regulating hormones. Lactate and IL-6 mediate the release of these hormones in animal/cell models and may provide a mechanistic link between exercise intensity and appetite regulation. The current study examined changes in appetite-regulating hormones, lactate, and IL-6 after different intensities of running. Eight males completed four experimental sessions: ) moderate-intensity continuous training (MICT; 65% V̇o); ) vigorous-intensity continuous training (VICT; 85% V̇o); ) sprint interval training (SIT; repeated "all-out" sprints); and ) Control (CTRL; no exercise). Acylated ghrelin, active glucagon-like peptide-1 (GLP-1), total peptide YY (PYY), lactate, IL-6, and appetite perceptions were measured pre-, immediately postexercise, 30 min postexercise, and 90 min postexercise. Energy intake was recorded over 3 days. VICT and SIT suppressed ghrelin ( < 0.001), although SIT elicited a greater ( = 0.016 vs. MICT) and more prolonged ( < 0.001 vs. all sessions) response. GLP-1 increased immediately after MICT ( < 0.001) and 30 min after VICT ( < 0.001) and SIT ( < 0.002), while VICT elicited a greater postexercise increase in PYY vs. MICT ( = 0.027). Postexercise changes in blood lactate and IL-6 correlated with the area under the curve values for ghrelin ( = -0.60, < 0.001) and GLP-1 ( = 0.42, = 0.017), respectively. Appetite was suppressed after exercise ( < 0.001), although more so after VICT ( < 0.027) and SIT ( < 0.001) vs. MICT, and energy intake was reduced on the day after VICT ( < 0.017 vs. MICT and CTRL) and SIT ( = 0.049 vs. MICT). These findings support an intensity-dependent paradigm for appetite regulation following exercise and highlight the potential involvement of lactate and IL-6. This study examines the involvement of two potential mechanisms (lactate and IL-6) that may explain the intensity-dependent effects of acute exercise on appetite-related parameters. Our findings support a clear intensity-dependent paradigm for appetite regulation following exercise, as highlighted by the change in acylated ghrelin and the suppression of appetite and energy intake after vigorous exercise (continuous and intermittent). Further, our findings extend previous work in animal/cell models by providing evidence for the potential role of lactate and IL-6 in mediating changes in appetite-related parameters following exercise in humans.