We have studied the possible mechanism of anti-asthmatic action of ethanolic extracts of driedseeds of Lepidium sativum (EXLS, 400 mg/kg) using various experimental models. EXLSproduced an increase in the Pre-Convulsion Dyspnoea time induced by histamine andacetylcholine 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 ascompared to the control rats. Treatment with EXLS also produced decrease in the elevatedhistamine release from the sensitized guinea-pig lungs. The anti-asthmatic anti-inflammatoryresponses of EXLS was supported by improvement in microscopic changes like infiltration ofinflammatory cells, submucosal edema, epithelial desquamation and reduced lumen size of thebronchi. The pD2 values of histamine in tracheal chain and taenia-coli were significantly greaterand that in lung strip was lower in the sensitized animals as compared to control. Treatment ofsensitized guinea pigs with EXLS significantly decreased pD2 values of histamine in all threepreparations. Our data suggest the prevention of hyper-responsiveness in bronchial smoothmuscles and inhibition of the immediate hypersensitive reaction, histamine release in the lungsand the infiltration of various inflammatory cells as the possible mechanisms of anti-asthmaticactivity of EXLS.