This study investigated the anti-inflammatory effects of wheat germ oil (WGO) on RAW 264.7 cells. It was shown that WGO had no cytotoxicity against the treated cells or negative effect on their proliferation. WGO suppressed nitric oxide (NO) secretion considerably and had inhibitory effects on the production of LPSinduced NO and pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β). In particular, the IL-6 and TNF α inhibition activities were over 90% at 100 μg/ml concentration of the oil. WGO also inhibited the LPSinduced expression of cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-kappa B (NF- κB), and reduced the expression of phosphorylated ERK and JNK. Moreover, the croton-oil induced edema in mouse ears was reduced by WGO, and no mortalities occurred in mice administered 5,000 mg/kg body weight of WGO over a 2-week observation period. In conclusion, these results provide evidence for the antiinflammatory effect of WGO that likely occurs via modulation of NF-κB and the JNK/ERK MAPK signaling pathway.