Although acclimatization to intermittent hypoxia (IH) improves exercise performance by increasing oxygen delivery/utilization, the effect of chronic IH on platelet-leukocyte interaction and inflammation-related cytokine secretion caused by strenuous exercise remains unclear. This investigation elucidates how two intensities of IH influence eosinophil- and neutrophil-platelet aggregation (EPA and NPA) as well as pro- and anti-inflammatory cytokines mediated by strenuous exercise. Twenty healthy sedentary men were randomly divided into severe (SIH) and moderate (MIH) intermittent hypoxia groups which were exposed to 12% O₂ (SIH) and 15% O₂ (MIH) for one hour/day, respectively, for five days/week for eight weeks in a normobaric hypoxia chamber. Before IH intervention, (i) exercise up to maximal oxygen consumption promoted shear-, lipopolysaccharide (LPS)-, and N-formyl-methionyl-leucyl-phenylalanine-induced EPA; increased interleukin (IL)-1and malondialdehyde (MDA) levels, and decreased total antioxidant level in plasma; (ii) exposure to 12% O₂, but not to 15% O₂, for one hour enhanced LPS-induced EPA and reduced plasma total antioxidant level. After IH for eight weeks, hypoxia- and exercise-promoted EPA, IL-1, or MDA levels were suppressed in both MIH and SIH groups, and plasma IL-6 and IL-10 levels in the SIH group were increased. However, the NPA induced by the shear force and chemical agonists was not changed under the two IH regimens. Therefore, both MIH and SIH regimens ameliorate eosinophil/platelet-related thrombosis, pro-inflammatory IL-1secretion, and lipid peroxidation enhanced by strenuous exercise. Furthermore, SIH simultaneously increases circulatory anti-inflammatory IL-6/IL-10 concentrations. These findings can help to develop effective IH regimens that improve aerobic fitness and minimize risk of thrombo-inflammation.