Peptic ulcer disease is one of the commonest gastrointestinal diseases in the world and several orthodox drugs have been employed for the treatment of this disease. Although effective, some of these drugs produce adverse effects with a great tendency for the disease to reoccur. Hence, the need for further screening of medicinal plants for potential antiulcer activity and as sources for antiulcer lead compounds. Andira inermis is one of the plants identified to be used traditionally in ulcer-related conditions. This research work was aimed at evaluating the peptic ulcer-protective effects of aqueous-methanol stem bark extract of A. inermis in rats with acetylsalicylic acid and cold stress-induced ulceration. Adult Wistar rats were grouped into 5 of five rats each. Rats in Group A were administered normal saline (30 ml/kg i.p) to serve as the negative control. Rats in groups B, C and D were pretreated with the graded doses of the extract (100, 200 and 400 mg/kg i.p). Rats in group E were treated with Cimetidine (100 mg/kg i.p) to serve as the positive control group. Thirty minutes post-treatment, ulceration was induced with acetylsalicylic acid (150 mg/kg p.o) and all the rats were subjected to cold restrain stress for a 4h period. The rats were then sacrificed humanely and their stomachs were excised for gross examination and scoring of ulcer indices. The mean ulcer indices, percentage severity of ulceration and percentage ulcer protection were determined using corresponding calculations. The results revealed that acetylsalicylic acid combined with cold stress caused mostly marked congestion, gross erosions and deep ulcers with ecchymotic and petechial hemorrhages on the gastric mucosa of the rats treated with normal saline (30 ml/kg i.p.). The aqueous methanol stem bark extract of A. inermis significantly (p < 0.05) inhibited the formation of these lesions. The extract caused increased secretion of mucous on the gastric mucosa of rats and a dose-dependent reduction in ulcer indices. This was significant (p < 0.05) at the dose of 400 mg/kg i.p of the extract. The extract, at graded doses of 100, 200 and 400 mg/kg i.p produced percent ulcer protection of 60.0%, 73.3%, and 80.0% respectively. This was comparable to Cimetidine which showed a percent ulcer protection of 86.7%. This shows that the stem bark extract of Andira inermis possesses gastro-protective effects and has the potential to be developed as an agent for the treatment of peptic ulcers..