TNF-alpha is considered to play a pivotal role in many inflammatory and illness states. In our previous study we found that nimesulide, a COX-2 selective inhibitor, prevents the lipopolysaccharide-induced elevation in plasma TNF-alpha in rats. The present study was undertaken to elucidate the effect of nimesulide on TNF-alpha levels in the paw exudate of rats pretreated with lipopolysaccharide (LPS). Rats were injected (subplantar) with LPS (100 mug/paw) in the right hind, which resulted in a prominent increase in paw exudate TNF-alpha levels, peaked at one hour post injection. In rats pretreated with nimesulide (30mg/kg, ip), the elevation in TNF-alpha in the paw exudate was significantly reduced, as compared to the LPS treated group. These results further stress the multiple antiinflammatory effects of nimesulide. (C) 2001 Elsevier Science Inc. All rights reserved.