This study aimed to determine whether 2 wk of high-intensity intermittent training (HIIT) altered inflammatory status in plasma and adipose tissue in overweight and obese males. Twelve participants [mean (SD): age 23.7 (5.2) yr, body mass 91.0 (8.0) kg, body mass index 29.1 (3.1) kg/m(2)] undertook six HIIT sessions over 2 wk. Resting blood and subcutaneous abdominal adipose tissue samples were collected and insulin sensitivity determined, pre- and posttraining. Inflammatory proteins were quantified in plasma and adipose tissue. There was a significant decrease in soluble interleukin-6 receptor (sIL-6R; P = 0.050), monocyte chemotactic protein-1 (MCP-1, P = 0.047), and adiponectin (P = 0.041) in plasma posttraining. Plasma IL-6, intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), IL-10, and insulin sensitivity did not change. In adipose tissue, IL-6 significantly decreased (P = 0.036) and IL-6R increased (P = 0.037), while adiponectin tended to decrease (P = 0.056), with no change in ICAM-1 posttraining. TNF-α, MCP-1, and IL-10 were not detectable in adipose tissue. Adipose tissue homogenates were then resolved using one-dimensional gel electrophoresis, and major changes in the adipose tissue proteome, as a consequence of HIIT, were evaluated. This proteomic approach identified significant reductions in annexin A2 (P = 0.046) and fatty acid synthase (P = 0.016) as a response to HIIT. The present investigation suggests 2 wk of HIIT is sufficient to induce beneficial alterations in the resting inflammatory profile and adipose tissue proteome of an overweight and obese male cohort.