The current study aimed to determine the protective effect of P. reticulatus on ethanol-induced gastric ulcer. For this purpose, thirty-six Sprague-Dawley rats were divided into six groups. The first group served as normal control, while, in other five groups, absolute ethanol was used to induce gastric ulcer. Group II served as a diseased group, while groups III, IV, and V were treated with methanol extract, ethyl acetate fraction, and n-hexane fraction, respectively, in a dose of 400 mg/kg bodyweight. Group VI was given omeprazole in a dose 20 mg/kg bodyweight. The stomachs were removed, ulcer score was evaluated, and histopathological examination of gastric lumen was conducted. Total acidity and pH values were determined in gastric juice. TNF-α and IL-8 mRNA expressions levels were determined using the reverse transcription real-time PCR method. The data indicated that P. reticulatus protected against gastric ulcer, which was evident by attenuation of ulcer score. The pretreatment with P. reticulatus raised the gastric pH and improved all evaluated histopathological parameters such as ulcer score, erosion score, hemorrhage score, fibrinoid necrosis score, inflammatory infiltrate score, and edema score. P. reticulatus significantly reduced mRNA expression levels of TNF-α and IL-8. In conclusion, P. reticulatus possess antiulcer property which might be attributed to downregulation of TNF-α and IL-8 expression levels.