We tested to determine if Mori Cortex Radicis extract has antioxidant activities and its potential mechanism of action was explored. Anti-oxidative effects were tested by measuring free radical and nitric Oxide (NO) scavenging activity, and reducing power. Since iNOS and COX-2 are important enzymes responsible for the production of free radicals in the cell, Mori Cortex Radicis extract was tested as to whether it could inhibit iNOS and COX-2 expression in LPS stimulated Raw cells. 70% methanolic extract of Mori Cortex Radicis exerted significant DPPH free radical and NO scavenging activities. In addition, the Mori Cortex Radicis extract exerted dramatic reducing power with maximal activity observed at 1 mg/ml (11-fold over control). Production of iNOS induced by LPS was significantly inhibited by the Mori Cortex Radicis extract, suggesting it could inhibit NO production by suppressing iNOS expression. COX-2 induced by LPS was also significantly inhibited by the Mori Cortex Radicis extract. The extract contains well known antioxidant components including phenolics, flavonoids and anthocyanin at the concentration of 0.23 mg/g, 42.97 mg/g and 12.08 mg/g, respectively. These results suggest that 70% methanolic extract of Mori Cortex Radicis exerts significant anti-oxidant activity via inhibiting iNOS and COX-2 induction.