Background Recent researches suggest that oxygen and its related species (oxidants) may contribute to the pathogenesis of a number of important lung diseases. Endogenous and exogenous reactive oxygen species play a major role in airway inflammation and are determinants of asthma severity. Aim The aim of this work was to study the antioxidant activity of nicorandil drug in bronchial asthma as an attempt to minimize the dose and side effects of using corticosteroids. Materials and methods The study was carried out in 50 rats weighing 120–150 g, subdivided into five groups each of which consisted of 10 rats. Group 1 rats were given normal saline intragastric and served as the control group; group 2 rats were given ovabumin; group 3 received dexamethasone 1 h before ovalbumin (OVA) challenge till last challenge (after 24 days); group 4 received nicorandil 1 h before OVA challenge till last challenge (after 24 days); group 5 received dexamethasone and nicorandil 1 h before OVA challenge till last challenge (after 24 days). At the end of the experiment (24 days), animals were kept on overnight fasting and were killed by decapitation. Lung sections were collected and then divided into two portions: one for histopathology and the other part of lung sections were homogenized and prepared for estimation of lung malondialdehyde, glutathione peroxidase, and tumor growth factor-β1 (TGF-β1). Blood samples were collected from all studied groups and lifted for clotting at 37°C and then centrifuged for separation of plasma for estimation of TGF-β1, tumor necrosis factor-α, and interleukin-6. Results The study showed that nicorandil administration whether alone or with dexamethasone, significantly reduced serum and tissue levels of inflammatory markers (TGF-β1, tumor necrosis factor-α, interleukin-6) and also significantly decreased lung malondialdehyde, TGF-β1 together with elevation of antioxidant activity presented by elevation of serum glutathione peroxidase.