Inflammatory mediators were markedly increased in sepsis (TNF-α, IL-6, HMGB1, TLR-4, and NF-κB; all <i>p</i> < 0.001 vs. Control) and significantly downregulated by pioglitazone (<i>p</i> < 0.01, <i>p</i> < 0.001, <i>p</i> < 0.001, <i>p</i> < 0.01, <i>p</i> < 0.01 vs. CLP + Saline, respectively). This evidence concerns the gene HMGB1 and Sepsis.