Objective To investigate the effects of antihistamine agents, loratadine and ketotifen, on the model of exercise-induced asthma in guinea pigs with lipopolysaccharide ( LPS) and metyapone. Methods Nineteen guinea pigs were injected peritoneolly with LPS (1mg/kg, i. p. ) and metyapone ( 50mg/kg, i. p. ). Then they were randomized into 3 groups. The control group ( n =7) did not take any drug, ketotifen group ( n =6) adminisd-1 ) for 4 days. On the fifth day, lung resistance (RL) and dynamic compliance of respiratory system (Cdyn) of 3 groups were measured before and after exercise challenge. The total number of leukocytes in bronchoalveolar lavage fluid (BALF) from 3 groups was counted and differentiated cell type count was measured. Morphometric examination of the animal lungs was performed. Results In control group, RLincreased and Cdyn decreased significantly after exercise challenge. In ketotifen group and loratadine group with no change. There was a significant increase in the number of neutrophils, macrophages and eosinophils in BALF from control group. The infiltration of neutrophils in the bronchial mucosa was shown in control group in the morphometric study. Conclusion Loratadine and ketotifen can inhibit the exercise-indaced bronchoconstriction in guinea pigs pretreated with LPS and metyrapone. Inhibiting the formation of inflammation in airway may be the therapeutic mechanism of these H-1 receptor antagonists.