Quinine remains an important anti-malarial drug. The 2010 World Health Organisation guidelines recommend a combination of quinine plus doxycycline, tetracycline or clindamycin as second-line treatment for uncomplicated malaria and also for treatment of malaria during first trimester of pregnancy. However, the effects of quinine on many gastrointestinal functions are not known. Therefore this study aims at investigating the effect of therapeutic dose of quinine on gastric acid secretion, which might be important in peptic ulcer patients. Forty albino Wistar rats were randomly divided in 8 groups of 5 animals each. Gastric acid output was measured by the continuous perfusion method in animals anaesthetized with 25g/100ml urethane at a dose of 0.6ml/100g body weight, i.p. After consistent basal gastric output were obtained, each animals in the different groups were treated as follows: group 1 received normal saline (1ml/kg, i.p) administration ; group 2, quinine (10mg/kg, i.m); group 3, carbachol (50μg/kg, i.p); group 4, quinine + carbachol; group 5, atropine (1mg/kg, i.p) + quinine; group 6, histamine (20mg/kg, i.p); group 7, quinine + histamine and group 8, ranitidine (4mg/kg, i.p) + quinine. Values were expresses as mean ± SEM and compared by student t-test. Result showed that peak acid secretion (PAS) in rats treated with normal saline was 1.28 ± 0.04mEq/L/10min. Quinine administration significantly increased the PAS to 2.00 ± 0.18mEq/L/10min (p < 0.01). Carbachol significantly increased PAS to 9.38 ± 1.33mEq/L/10min (p < 0.001). Injection of quinine before carbachol did not significantly affect the PAS as compared with carbachol alone (p > 0.05) and atropine administration did not significantly reduce the PAS to quinine (p> 0.05). Histamine significantly increased the PAS to 8.08 ± 0.26mEq/L/10min (p <0.001). Injection of quinine before histamine significantly reduced the PAS to 3.42 ± 1.12mEq/L/10min (p < 0.01) and ranitidine blocked the secretory response of the stomach to quinine. In conclusion, quinine increased gastric acid secretion in rats by stimulating histamine H2 receptors.