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Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. Some studies have indicated that HES may have anti-inflammatory effects. The presentin vivostudy was performed to investigate the effects of HES on hepatic production of cytokines and activation of transcription factors in sepsis.Adult male Sprague-Dawley rats were randomly divided into four groups: rats challenged with lipopolysaccharide (LPS) (5 mg kg−1) and treated with saline (64 ml kg−1); challenged with LPS (5 mg kg−1) and treated with HES (16 ml kg−1); injected with saline and treated with HES (16 ml kg−1); and saline control. Each hepatic tissue was collected in groups of rats 2 h after induction of endotoxemia for determination of tumour necrosis factor (TNF)-α levels, TNF-α mRNA expressions, and nuclear factor (NF)-κB, activator protein (AP)-1 activities or 3 h after LPS challenge for IL-1β, IL-6, IL-8, IL-10 levels and the mRNA expressions.Endotoxemia was associated with significant increases in hepatic proinflammatory cytokine productions and transcription factor activities. HES significantly reduced the increased hepatic levels of TNF-α, IL-1β, IL-6, IL-8 and the mRNAs in the endotoxemic rats. Similarly, HES could inhibit hepatic NF-κB and AP-1 activations.The results suggest that in sepsis HES may down-regulate hepatic inflammatory mediators production and these anti-inflammatory effects may act through inhibition of NF-κB and AP-1 activations. [ABSTRACT FROM AUTHOR]