OBJECTIVE: This study examines the pro-inflammatory action caused by subcutaneous (s.c.) injection of the bee venom (BV) Apis melifera in the rat paw. METHODS: Male Wistar rats were used. The venom of Apis melifera was injected s.c. into the rat paw and the oedema formation and the activity of myeleperoxidase (MPO) were measured. RESULTS: Subcutaneous injection of BV caused dose-and time-dependent paw oedema (ED50 of 1.5 microg/paw) with peak at 30 min. The MPO activity increased about 1.6, 4.2 and 8.9 folds at 0.5, 4 and 6 h after s.c. injection of BV. The mast cell degranulating drug 48/80, pyrilamine or metysergide, inhibited BV-mediated oedema formation (88, 62 and 96%, respectively). Likewise, L-NAME, the NK1 antagonist FK 888, the B1 des-Arg9-[Leu8]-BK or B2 kinin antagonist Hoe 140 also antagonised the paw oedema induced by BV (60, 59, 49, and 49%, respectively). SR48968 and SR14280, respectively NK2 and NK3 antagonists and also indomethacin, inhibited by 31, 29 and 22%, respectively BV-induced oedema formation. In contrast, the PAF antagonist WEB 2086 or valeryl salycilate, did not affect the BV-induced paw oedema. The levels of MPO were inhibited by compound 48/80, cyproheptadine, Hoe 140, or by des-Arg9[Leu8]-BK (85, 61, 59, and 53%, respectively) measured 6 h after. CONCLUSION: These results indicate that the BV from Apis melifera causes a marked dose-and time-dependent oedema formation in the rat paw, an effect that is accompanied by intense leukocyte migration. The pro-inflammatory response induced by BV is mediated by several mechanisms, namely the release of histamine and/or serotonin from mast cells, activation of H1 histamine receptor, production of nitric oxide, the involvement of kinins through the activation of B1 and B2 receptors, and also tachykinins acting at NK1 receptor or and to a lesser extent at NK2 and NK3 receptors.