Kolaviron, isolated from Garcinia kola seed (Family: Guttiferae), is known for numerous medicinal and therapeutic values. The anti-ulcer, anti-inflammatory and antioxidant properties of Garcinia kola seed have been reported. The main mechanisms through which kolaviron exert its anti-secretory with cytoprotective potential has not been elucidated. So, the present research work therefore evaluated anti-secretory and cyto-protective potentials of the anti-ulcer properties of kolaviron using different ulcer models in rats. Cold-restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models were used to assess its anti-ulcerogenic activity in rats. KV’s effects on gastric juice for free and total acidity, peptic activity and mucin secretion were evaluated. The H+,K+-ATPase activity was assayed in gastric microsomes, spectrophotometrically. In CRU model, which is the basic model for screening anti-ulcer agent, KV (100, 150 and 200mg/kg, p.o.) showed percentage protection of 52.1%, 53.5% and 69.0% (P<0.01) respectively while omeprazole (10mg/kg, p.o.) showed a protection of 84.6% (P<0.001) with reference to the control group. In ASP and PL -induced gastric ulcer model, KV (200mg/kg, p.o.) showed protection index of 68.6% and 67.6% (P<0.01) respectively, whereas omeprazole (10mg/kg, p.o.) exhibited 84.3% and 69.0% (P<0.01) protection respectively. KV (200mg/kg, p.o.) produced 51.5% (P<0.01) protection against gastric mucosal damage, induced by absolute alcohol. Sucralfate (500 mg/kg, p.o.) exhibited 76.3% (P<0.001) protection under the same condition, when compared with the control group. Likewise, KV (200mg/kg, p.o.) reduced free acidity, total acidity and peptic activity by 32.6%, 56.2% and 35.4% (P<0.05) respectively, while omeprazole (10mg/kg, p.o.) significantly reduced free acidity, total acidity and peptic activity by 61.8%, 69.9% and 46.7% (P<0.01) respectively, compared with the control group. The same dose of KV and omeprazole (10mg/kg, p.o.) increased the mucin secretion by 40.1% and 47.9% (P<0.01) respectively, compared with the control. The incubation of KV (60-100µg/ml) with the microsomes, inhibited the inorganic phosphate release from gastric proton pump activity proportionately from 17.2% (288.3µM/hr/mg protein) to 74.3% (89.5µM/hr/mg protein) respectively, with IC50 of 43.8µg/ml. Likewise, omeprazole (10-50µg/ml) inhibited the enzyme from 12.5% (304.5µM/hr/mg protein) to 87.5% (87.0µM/hr/mg protein) respectively, with IC50 = 32.3µg/ml. Kolaviron possesses anti-ulcer activity against experimentally-induced peptic ulcer models and exhibited a proton pump inhibitory activity. So, it has both cyto-protective and anti-secretory potentials. Hence, kolaviron may emanate as a potent anti-ulcer compound.