Outbred OF1 mice infected in a first step with a mouse-adapted Helicobacter pylori strain were immunized in a second step by systemic or mucosal routes: systemic immunizations were performed subcutaneously with adjuvanted urease either in the infra or supra-diaphragmatic region of the body, while mucosal immunization was done with urease in the presence of E. coli heat Labile toxin. Mucosal and subcutaneous immunizations induced in infected mice a significant reduction in bacterial density whatever the site of injection but complete eradication was preferentially observed in mice immunized subcutaneously in the back. Systemic immunization with appropriate schedules and formulations could constitute a valuable approach to cure Helicobacter pylori infection.