Diabetic patients and animals show an increased susceptibility to bacterial infections due to impaired bactericidal function of various host-defense mechanisms. In our study, we examined the ability of alveolar macrophages (AMs) of the diabetic BB rat to phagocytize and kill Staphylococcus aureus bacteria. Groups of spontaneously diabetic BB rats with variable severity of diabetes were used and compared with non-diabetes-prone BB rats. AMs obtained from diabetic insulin-deficient BB rats showed a markedly decreased capacity to phagocytize and kill bacteria, a defect that was partially corrected after a period of aggressive insulin treatment. Glucose-intolerant BB rats and diabetes-prone BB rats who did not develop diabetes showed a normal AM function compared to non-diabetes-prone BB rats. The impaired phagocytotic and bactericidal functions of AMs appeared to be caused by a cellular abnormality associated with the degree of insulin deficiency.