This study aimed to elucidate the antiinflammatory mechanism of grape-seed acetone extract (GSAE) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The GSAE at the highest concentration (500 ${mu}g/mL$) significantly inhibited nitric oxide production by approximately 78% and suppressed inducible nitric oxide synthase protein expression by approximately 83% compared to LPS-stimulated cells. The GSAE also suppressed inhibitor ${kappa}B{alpha}$ phosphorylation and nuclear factor-${kappa}B$ (NF-${kappa}B$; p65) transcriptional activity and translocation to the nucleus. In addition, GSAE induced the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner, and that blocking HO-1 activity eliminated the inhibitory effects of the GSAE. The addition of carbon monoxide, a byproduct of heme degradation by HO-1, mimicked the inhibitory action of low concentrations of GSAE. These data suggest that GSAE carries out anti-inflammatory actions in macrophages through the induction of HO-1 and suppression of NF-${kappa}B$ activation.