The present study was undertaken to test the hypothesis of possible inhibitory effect of nimesulide (4-nitro-2-phenoxymethane-sulfoxide) on plasma TNF-α level. Male Sprague-Dawley rots were injected intraperitoneally (ip) with E. coli lipopolysaccharide (LPS; 1 mg/kg), which resulted in a dramatic increase in plasma TNF-α level peaked 60 min post injection (3890 ± 280 pg/ml, compared to undetectable values in the control group). Nimesulide (30 mg/kg) injected ip 60 min prior to LPS, prevented LPS-induced elevation in plasma TNF-α. Nimesulide alone did not alter circulating levels of TNF-α. It appears that the anti-inflammatory properties of nimesulide may in part be attributed to its inhibitory effect on TNF-α production.