Abstract： To investigate the role of histamine in airway remodeling, 50 healthy guinea pigs were divided into 5 groups: control group:nebulized inhalation of distilled water for 8 weeks; asthma model group: nebulized inhalation of ovalbumin (OVA) for 8 weeks after sensitization; continued asthma model group: nebulized inhalation of OVA for 14 weeks after sensitization; histamine group: nebulized inhalation of OVA for 14 weeks after sensitization and histamine was added in the last 6 weeks; antagonist group: nebulized inhalation of OVA for 14 weeks after sensitization and histamine receptor antagonists were added in the last 6 weeks. For each group, the concentration of histamine, sodium ion (Na+), chlorine ion (Cl-), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), pH, actual bicarbonate (AB), standard bicarbonate (SB) in serum, and thickness of airway mucosa, base membrane and smooth muscle were measured and compared with each other. The results showed that: (1) the concentration of histamine in serum and the thickness of airway increased, the following order was, the control group, the asthma model group, the continued asthma model group and histamine group (P＜0.01); and the concentration of histamine in serum and the thickness of airway of antagonist group was lower than that of the continued asthma model group (P＜0.05, 0.01). (2) PaO2 of the asthma model group was lower than that of the normal control group (P＜0.01); PaO2, pH, AB, SB decreased, the following order was, the asthma model group,the continued asthma model group and the histamine group (P＜0.01); and PaO2, pH, AB, SB of the antagonist group was higher than that of the continued asthma model group (P＜0.01); but for PaCO2, the order was converse (P＜0.01); For the concentration of Na+ and Cl- in serum, there was no difference among these groups. It is concluded that: (1) Histamine is one of the mediators in the airway remodeling of asthma. (2) Histamine receptor antagonists may play a role in preventing and treating airway remodeling. (3) There is a negative correlation between the PaO2, pH and the wall thickness of the airway (P＜0.01), while a positive correlation between the PaCO2, anion gap (AG) and the wall thickness of the airway (P＜0.01).