Summary Aqueous extract of Ocimum canum Sim, (Lamiaceae) is used by some Ghanaians to manage diabetes mellitus. In vivo modulation of levels of fasting blood glucose by O. canum extract was evaluated in type-II diabetes mellitus using the C57BL/KsJ db/db genetically diabetic animal model, and its effects on glucose-stimulated insulin release in vitro were monitored using isolated rat pancreatic β-islet cells. The results showed that fasting blood glucose levels and body weight decreased significantly (p < 0.05) in diabetic and non-diabetic C57BL/KsJ mice, which were administered aqueous extract of O. canum. In vitro, the O. canum extract significantly enhanced insulin release from isolated rat pancreatic β-islet cells. Insulin release was found to be dependent on glucose concentration and increased with increasing O. canum concentration in the incubation medium up to an optimum extract concentration of 0.03 mg/ml. Release of the hormone decreased beyond this concentration of extract in the medium. Addition to the medium of Desmodium adscendens, a plant preparation used to manage inflammatory disorders, did not increase but rather inhibited insulin secretion by the pancreatic β-islet cells. These results could explain the use of O. canum in Ghanaian folk medicine to manage diabetes mellitus.