Rosmanol is a natural polyphenol from the herb rosemary (Rosmarinus officinalis L.) with high antioxidant activity. Rosmanol markedly inhibited LPS-stimulated iNOS and COX-2 protein and gene expression, as well as the downstream products, NO and PGE2 in RAW 264.7 cells. Treatment with Rosmanol also reduced translocation of the nuclear factor-κB (NF-κB) subunits by prevention of the degradation and phosphorylation of inhibitor κB (IκB). Rosmanol exerted significant antinociceptive effects in both hot plate and tail immersion tests at the dose level of 10-100 mg/kg. The cellular and neural mechanisms underlying pain responses elicited involve interplay of a number of neurotransmitters and ion channel, and the central analgesic effects of Rosmanol were not antagonized by the opioid receptor antagonist naloxone. This indicates that the central analgesic effects of Rosmanol may be exerted via one or more of several proposed nonopioid mechanisms such as blockade of voltage-gated Na+ channels, activation of the noradrenergic inhibitory system, enhancement of GABAergic and/or serotonergic systems. The physiological and toxicological properties of this compound have not been evaluated in humans.