Sesame oil is commonly used as antioxidant. Sesamin (SA) and sesamolin (SO) are major lignans (a non-fat constituent) in sesame seed oil, inhibit Δ5-desaturase activity and cause accumulation of dihomo-γ- linolenic acid (DGLA), a precursor of 1-series prostaglandins, and the decreasing production of proinflammatory 2-series prostaglandins and 4-series leukotrienes. Diets supplemented with SA and/or SO, lower serum levels of interleukin (IL)-1β, IL-6 but elevate IL-10 in mice after lipopolysaccharide (LPS) exposure. Mice fed with sesame seed oil have a 65% survival rate after cecal ligation and puncture as compared with the 20% survival in the controls. SA and SO inhibit the IL-6, tumor necrosis factor (TNF)-α and nitric oxide (NO) productions from microglia under LPS stimulation. The protective effects of SA/SO to stroke-prone spontaneously hypertensive rats and hepatic ischemia-reperfusion injury have been attribute to their antioxidant and anti-inflammatory activities. The antioxidant activities of SA/SO are identified in their methylenedioxyphenyl moieties that can be changed into dihydrophenyl (catechol) moieties. Since reactive oxygen species (ROS) are mediators of a variety of pathological processes, including inflammation and ischemic/hypoxic injury, the ROS scavenging moiety may contribute as an important component to prevent cells from the free radical injury. Hypoxia or HO-induced cell injury are related with activated MAPKs and caspase-3 activities. Evidence suggests that the protective effects of SA and SO on hypoxic neuronal cells are related to suppression of ROS generation and mitogen-activated protein kinases (MAPKs). In addition, SA/SO significantly reduce LPS-activated p38 MAPK. Specific inhibitors of MAPKs dose-dependently inhibit NO and cytokine productions in LPS-stimulated microglia. Therefore, the inhibition of NO and cytokine productions may partly due to the reduction of LPS-induced p38 MAPK signal pathway by SA and SO.