We have studied the possible mechanism of anti-asthmatic action of ethanolic extracts of dried seeds of Lepidium sativum (EXLS, 400 mg/kg) using various experimental models. EXLS produced an increase in the Pre-Convulsion Dyspnoea time induced by histamine and acetylcholine aerosol, a significant reduction in the elevated leucocyte counts in the Broncho-Alveolar Lavage fluid of sensitized guinea-pigs and reduction in the paw edema volume as compared to the control rats. Treatment with EXLS also produced decrease in the elevated histamine release from the sensitized guinea-pig lungs. The anti-asthmatic anti-inflammatory responses of EXLS was supported by improvement in microscopic changes like infiltration of inflammatory cells, submucosal edema, epithelial desquamation and reduced lumen size of the bronchi. The $pD_2$ values of histamine in tracheal chain and taenia-coli were significantly greater and that in lung strip was lower in the sensitized animals as compared to control. Treatment of sensitized guinea pigs with EXLS significantly decreased $pD_2$ values of histamine in all three preparations. Our data suggest the prevention of hyper-responsiveness in bronchial smooth muscles and inhibition of the immediate hypersensitive reaction, histamine release in the lungs and the infiltration of various inflammatory cells as the possible mechanisms of anti-asthmatic activity of EXLS.