We performed these studies to determine whether sialic acid (SIA) existed in the inflammatory exudate of the carrageenin (Car)-air pouch model and to elucidate the mechanisms of the antiinflammatory action of SIA on the Car-induced edema in rat hind paws. SIA (113.20 +/- 10.73 micrograms/ml) was detected in the exudate of Car-air pouch, and the plasma SIA (660.29 +/- 29.38 micrograms/ml) in Car-air pouch rats was significantly higher than that (490.00 +/- 29.37 micrograms/ml) in control rats. SIA (300 mg/kg, s.c.) suppressed the delayed phase of Car-induced edema, and it also suppressed the edema induced by Car plus arachidonic acid, Car plus PGE2, and bradykinin plus PGE2. However, SIA did not affect the edema induced by dextran, histamine, bradykinin, and Car plus PGE1. SIA affected neither the PG production in rats nor the [3H]PGE2-receptor binding of guinea pig ileum, and SIA reduced the PGE2-induced contraction of isolated guinea pig ileum. The above results suggest that SIA induces the antiinflammatory effects via its antagonism against PGE2. Furthermore, the presence of SIA in the inflammatory exudate and the higher concentration of SIA in the plasma than in the exudate might suggest that SIA plays patho-physiologically protective roles in inflammatory states.