Background Asthma is a chronic inflammatory disease of the airway characterized by airway hyper-responsiveness. It is caused by numerous cells, cytokines and mediators. Brain has traditionally been regarded as an immunologically privileged organ. This viewpoint has been based on the presence of meninges and a tight blood-brain barrier(BBB). Asthma has been considered as a chronic inflammatory disease in periphery. With the research development to asthma, it has find that asthma is not a "Free-standing event" of "independent organ" in periphery, multiple mechanism including central nervous system (CNS) take part in the pathophysiological changes of asthma. Now more and more researchers pay attention to the relationship between CNS and asthma. Leukotrienes and histamine are important mediators, which not only exist in periphery but also in CNS. Recent researchs show that leukotriene B_4 (LTB_4) content in cerebral cortex and lung tissue are increased in an asthmatic model of rat, and histamine content in cerebral cortex are increased in asthmatic guniea pigs, but to date there still no report about their effect in brain on asthma function. To explore if LTB_4 and histamine present regulatory effects on asthma-like reaction in rats, which help to understand themechanism of asthma, we take this program.Objective To investigate regulation effects of leukotriene B4 and histamine onbronchoconstriction and airway inflammation induced by antigen in an asthmaticmodel of rat.Methods Ovalbumin sensitized and challenged male SD rats were used asasthmatic model. Leukotriene B4, selective BLTi receptor antagonist U-75302 andhistamine were administrated intracerebroventricularly in the asthmatic model of rat,the airway resistance(RL) and dynamic lung compliance(Cdyn) before and afterantigen-challenged were observed. The total white cell and differential cell count inbronchoalveolar lavage fluid(BALF) were performed. Inflammatory cells infiltrationwere determined by lung pathological section.Results 1, Leukotriene B4 and histamine by icv inhibited the increase in Rl and thedecrease in Cdyn induced by antigen challenge. After pretreatment of U-75302intracerebroventricular injection, lung resistance increased and lung compliancedecreased.2> Leukotriene B4 and histamine by icv significantly reduced total white cell and the number of eosinophil and neutrophil. Leukotriene B4 and histamine also inhibited eosinophil infiltration below airway mucosa and around blood vessel. Conclusion 1 ^ Leukotriene B4 by icv inhibit bronchoconstriction and airway inflammation, and its antagonist U-75302 reverse the regulatory effect of leukotriene B4. These results indicate that leukotriene B4 in central nervous system may have negative feedback regulatory effects on asthma-like reaction in rats.2 -, Histamine by icv inhibit bronchoconstriction and airway inflammation, suggesting that the increased histamine in central nervous system may have regulatory effects on asthma-like reaction in rats.