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Excessive oxidative stress and chronic inflammation are implicated in the pathogenesis of chronic inflammation diseases. The purpose of this study was to determine whether the antioxidant and anti-inflammatory effects of Busan-grown <i>Agarum cribrosum</i> ethanol extract (ACE) and its organic solvent five fractions are exhibited in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. ACE and its five fractions from ACE evaluated the total antioxidant activity and the effect of pro-inflammatory cytokines and antioxidant genes expression in LPS-induced RAW 264.7 macrophages. ACE and its ethyl acetate (EtOAc) fraction showed a high total phenolic content and total antioxidant capacity by decreasing free radicals scavenging activity. ACE and its EtOAc fraction significantly repressed LPS-induced tumor necrosis factor α and interleukin-1β gene expression. Additionally, ACE and its EtOAc fraction significantly diminished the LPS-stimulated gene expression of inducible nitric oxide synthase and cyclooxygenase 2 genes with a concomitant decrease in their protein levels in the macrophages. The gene expression of NADPH oxidase 2 was significantly abolished by ACE and its EtOAc fraction in LPS-induced macrophages, while other antioxidant genes showed minimal effects. The results suggest that ACE and its EtOAc fraction exert inhibitory effects on LPS-stimulated inflammation and oxidative stress in macrophages accompanied by total antioxidant activity.