Many factors influence the inflammatory responses in rat trachea, including inflammatory mediators released from nerve fibers, histamine released by mast cells and endotoxin from the cell walls of bacteria. The inflammatory responses include plasma extravasation, subepithelial edema, and hypersecretion of secretory cells. But the mechanism of inflammation mediated by these factors was not completely understood. In the present study, a high dose of histamine was administered intravenously to induce the inflammation in rat airway. India ink was also injected as a tracer to label the leaky blood vessels in different time points. To investigate the serous cell secretion and subepithelial edema formation, the treacheal tissue was processed for histological study. Electron microcopy was carried out to investigate the ultrastructure of serous cells. To investigate the mechanism of histamine effect, the muscarinic receptor antagonist atropine (1 mg/ml/kg) or histamine H1 receptor antagonist mepyramine (10 mg/ml/kg) was injected 15 min before histamine injection. Five minutes after histamine, plasma leakage and serous cell secretion were extensive. The area density of India ink-labeled leaky vessels was 17.24 % ¡Ó 2.03 %. Saline, the vehicle of histamine, produced only a little extravasation. Mepyramine inhibited the histamine-induced plasma extravasation and serous cell degranulation significantly but atropine had no effect. The results suggest that histamine-induced serous cell degranulation is mainly through histamine H1 receptors but not through cholinergic muscarinic receptors in rat trachea.