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Histamine is widely distributed in the lungs and increases capillary permeability and P-selectin expression. To observe the role of histamine in acute lung injury (ALI), we measured the histamine and protein concentrations and cell numbers in the bronchoalveolar lavage (BAL) of LPS-induced ALI in rats. We instilled LPS (3 mg/kg) intratracheally, in conjunction with the intravenous histamine receptor antagonists (mepyramine, a H1-receptor antagonist, or ranitidine, a H2-receptor antagonist). LPS increased protein concentration and neutrophil numbers in the BAL as well as myeloperoxidase (MPO) activity in lungs after 6 h. LPS also increased histamine concentration in BAL after 2 h. Mepyramine and ranitidine attenuated the increased histamine concentrations. Total cell number in the BAL and MPO activity in the lungs were significantly decreased and neutrophil numbers and protein concentration in the BAL seemed to decrease with the administration of ranitidine at 6 h. In conclusion, endogenous histamine might be involved in the recruitment of neutrophils and protein leaks in LPS-induced ALI via the H2 receptors.