Objective:To explore the effect of neural histamine in the tuberomammillary nucleus (TM) on neurogenic pulmonary edema (NPE) onset in rabbits and the function of the rostral ventrolateral medulla (RVLM) in the neural histamine modulation of NPE. Methods: NPE was produced by the intracisternal injections of fibrinogen and thrombin. The contents of histamine in the TM and RVLM in rabbits were measured with high performance liquid chromatography (HPLC). Rabbits were placed on a stereotaxic frame and microinjection cannulae were inserted into the TM and RVLM using brain atlas coordinates. Animals were pretreated with R-α-methylhistamine (MeHA) in the TM and chlorphenamine Mmaleate/cimetidine in the RVLM prior to establishing the NPE model. Changes in the lung water ratio and mean arterial pressure (MAP) were recorded, and paraffin sections of lung tissue were observed by light microscope. Results: We found that the contents of histamine (HA) in the TM and RVLM increased significantly with the onset of NPE. Pretreatment with MeHA in the TM and chlorphenamine Mmaleate in the RVLM significantly decreased MAP, and the lung water ratio and histological characteristics of the NPE in the rabbit model. Pretreatment with cimetidine in the RVLM had no effect on NPE.Conculsion:The results suggest that neural histamine in the TM is involved in the onset of NPE, and this effect of neural histamine is mediated by H1 receptor in the RVLM.