Background: Indomethacin is an effective NSAID used in inflammation treatment. However, it causes gastric mucosal lesions. Alpha lipoic acid (ALA) is an antioxidant that prevents cell damage. Aim of the work: To detect the protective role of ALA on indomethacin-induced gastric mucosal alterations. Material and Methods: A total number of thirty adult male albino rats were randomly equally divided into three groups: control group (received distilled water), indomethacin-treated group; received 50 mg/kg b.w of indomethacin., once orally and ALA + indomethacin - treated group; received 100 mg/kg b.w. of ALA, orally for 3 days followed by once administration of 50 mg/kg b.w. of indomethacin, orally 1h after the last dose of the ALA. Four hours after indomethacin administration. The rats were anesthetized, sacrificed and the stomach immediately removed and processed for histological (light and electron microscopic) and inducible nitric oxide synthase (iNOS) immunohistochemical examination. Area % of collagen fibers and iNOS of all animal groups was measured and compared. Results: Indomethacin induced gastric mucosal erosion, degeneration, vacuolization, inflammatory cell infiltration, interstitial hemorrhage, blood vascular congestion and dilatation, deposition of collagen fibers and strong positive iNOS immunoreactivity. Area % of collagen fibers and iNOS was significantly increased in indomethacin-treated group when compared to control. ALA + indomethacin-treated group exhibited nearly normal histological, immunohistochemical and morphometric findings. Conclusion: ALA has a gastroprotective role as it can prevent the deleterious effects of indomethacin on the gastric mucosa.