Exercise suppresses appetite in an intensity‐dependent manner partly due to changes in peripheral appetite‐regulating hormones. While the underlying mechanisms are unclear, lactate release from active musculature may be important as its binding to gastric cell lines inhibits the release of the orexigenic hormone ghrelin. The contraction‐induced myokine interleukin‐6 (IL‐6) may also be involved, as it stimulates the production and release of anorexigenic factors such as glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY) from intestinal cells. If these mechanisms contribute to the intensity‐dependent suppression of appetite following exercise, post‐exercise increases in lactate and IL‐6 should coincide with changes in ghrelin, GLP‐1, and PYY. To test this hypothesis, the current study examined changes in blood lactate, IL‐6, and appetite‐regulating hormones in response to running at various intensities. Eight males performed four experimental sessions: 1) Moderate‐intensity continuous training (MICT, 30 min at 65% VO2max); 2) High‐intensity continuous training (HICT, 30 min at 85% VO2max); 3) Sprint interval training (SIT, 4 × 30 sec maximal efforts, 4 min rest); 4) Control (CTRL, no exercise). Lactate, IL‐6, ghrelin, GLP‐1, and PYY concentrations were measured pre‐, post‐, 30 min post‐, and 90 min post‐exercise. Appetite perceptions were assessed at the same time‐points using a visual analog scale. Exercise suppressed ghrelin and appetite in an intensity‐dependent manner (HICT and SIT vs. CTRL, p<0.001), with SIT resulting in a greater (SIT vs. MICT at 30 min post‐exercise, p<0.020) and more prolonged (SIT vs. all other sessions at 90 min post‐exercise, p<0.005) response. GLP‐1 increased immediately after MICT (p<0.001 vs. all other sessions) and at 30 min post‐exercise after HICT (p<0.002 vs. all sessions) and SIT (p=0.001 vs. CTRL). PYY increased immediately post‐exercise (p<0.001 vs. CTRL) though more so after HICT versus MICT (p=0.027). Exercise‐induced changes in appetite‐regulating hormones correlated significantly (p<0.009) with appetite perceptions (ghrelin: r=0.40; GLP‐1: r=−0.31; PYY: r=−0.36). Post‐exercise increases in blood lactate correlated negatively (p<0.036) with ghrelin (MICT: r=−0.43; HICT: r=−0.50; SIT: r=−0.45) and appetite (MICT: r=−0.43; HICT: r=−0.47; SIT: r=−0.45). Changes in IL‐6 correlated with GLP‐1 following SIT only (r=0.48, p=0.018), though no relationship between IL‐6 and PYY was observed. These findings support an intensity‐dependent paradigm for appetite regulation following exercise, which appears to be closely associated with reductions in ghrelin though increases in GLP‐1 and PYY also contribute. The results also highlight the potential involvement of lactate and IL‐6 in mediating changes in appetite‐regulating hormones, particularly after intense exercise.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada