We investigated the occurrence and the role of HSF1 activation and inducible hsp72 expression in the carrageenin pleurisy in the rat. Molecular analysis performed on pleural cells collected from rat pleural cavity after carrageenin challenge revealed increased HSF1 activation and hsp72 expression. Moreover, local injection of a double-stranded oligodeoxynucleotide (ODN) containing the heat shock element sequence, acting as transcription factor decoy, exacerbated the inflammatory reaction. The exacerbation, induced by wild-type, but not by mutant ODN decoy, was associated to both inhibition of HSF1/DNA binding activity and reduction of hsp72 expression. In conclusion, this study shows that HSF1 activation and hsp72 expression both actually occur in acute inflammation and that the remission of the inflammatory reaction is tightly associated to the HSF1-dependent hsp72 expression, suggesting a a relevant role for the HSF1/hsp72 pathway as an endogenous anti-inflammatory system.