Bacterial infections in the respiratory tract and middle ear continue to be a major cause of morbidity and mortality despite the availability of antibiotic therapies. To assist development of vaccines for preventing these infections, animal models have been established in rodents. These models have been used effectively to evaluate different vaccination strategies. Our studies have found that for respiratory tract infections caused by Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis, a primary immunisation targeted to the gut-associated lymphoid tissue was extremely effective in enhancing bacterial clearance. For the gram-negative pathogens, NTHI and M. catarrhalis, this mucosal immunisation was significantly more effective than systemic immunisation, however, for S. pneumoniae systemic immunisation was as effective. A strategy using these models has effectively been used to determine the potential of antigens from each of the pathogens to protect against infection. Antigens that demonstrate significant vaccine potential have been used to investigate delivery systems. One of the major challenges that still exists is to find mechanisms that will effectively deliver protein antigens to mucosal surfaces. Several strategies have been investigated and resulted in varying degrees of success.