The importance of lung tissue in asthma pathophysiology has been recently recognized. Although nitric oxide (NO) mediates smooth muscle tonus control in airways, its effects on lung tissue responsiveness has not been previously investigated. We hypothesized that chronic NOS inhibition by N-nitro-L-arginine methyl ester (L-NAME) may modulate lung tissue mechanics, eosinophil and extracellular matrix remodeling in guinea pigs with chronic pulmonary inflammation. Animals were submitted to seven saline or ovalbumin exposures with increasing doses (1~5mg/mL-4weeks) and treated or not with L-NAME in drinking water. Seventy-two hours after the seventh inhalation, animals were anesthetized, exsanguinated, and oscillatory mechanics of lung tissue strips were performed in baseline condition and after ovalbumin challenge (0.1%). Using morphometry, we assessed the density of eosinophils, nNOS and iNOS-positive distal lung cells, smooth muscle cells as well as collagen and elastic fibers in lung tissue. Ovalbumin-exposed animals had an increase in baseline and maximal tissue resistance and elastance, eosinophil density, nNOS and iNOS-positive cells, the amount of collagen and elastic fibers and isoprostane-8 PGF2 expression in the alveolar septa compared to controls (P<0.05). L-NAME treatment in ovalbumin-exposed animals attenuated lung tissue mechanical responses (P<0.01), nNOS and iNOS-positive cells, elastic fiber content (P<0.001) and isoprostane-8-PGF2 in the alveolar septa (P<0.001). However, this treatment did not affect the total number of eosinophils and collagen deposition. These data suggest that NO contributes to distal lung parenchyma constriction and to elastic fibers deposition in this model. One possibility may be related to the effects of NO activating the oxidative stress pathway.