In this study, ischemia-reperfusion caused increased leukocyte adhesion and emigration to a greater extent in the diabetic rats compared to control rats, even though no differences in the PF-04217903 number of adherent and emigrated leukocytes were seen under basal conditions prior injury between groups. However, in another study of alloxantreated rats, a decrease in leukocyte-endothelial cell interactions in the internal spermatic fascia after inflammatory challenge was demonstrated. An important discrepancy between the former study in alloxan-treated rats and the present study in mice is the time period of severe hyperglycemia, as longer hyperglycemic periods correlate with higher degree of for instance protein glycosylation that in turn might impair immune responses as well as other body functions. In our study, mice had been hyperglycemic for only 3�? days prior the inflammatory challenge, while the rats had been confirmed hyperglycemic for 33 days after alloxan injection. To expand our results of acute leukocyte recruitment, bacterial clearance was studied in a clinically relevant infection model in severely hyperglycemic mice, in which the leukocyte recruitment effect was most prominent. We found that the alloxan-treated mice showed decreased ability to totally clear the bacterial infection compared to control mice, despite a greater initial decrease of bacteria post-infection and increased number of recruited neutrophils to the infected area. These results are in line with clinical findings in diabetic patients, as bacterial infections are abundantly occurring complications of the disease, and are in accordance with a previous experimental study of S. aureus injected in the hindpaw of non-obese diabetic mice. However, NOD mice display numerous other immune abnormalities such as autoimmune thyroiditis, autoimmune peripheral polyneuropathy as well as systemic lupus erythematosus-like disease which most probably also affect inflammatory responses needed for bacterial clearance, thus influencing the results of this study. Impaired bacterial clearance in NOD mice was attributed to decreased tissue levels of MIP-2 at the site of infection, resulting in decreased leukocyte recruitment. However, whether this defect in MIP-2 secretion is due to the diabetic stage or the immune defect in NOD mice is uncertain. The initial drop of bacterial luminescence observed in the diabetic mice could reflect increased numbers of recruited leukocytes, or an increased ability to initially kill inoculated bacteria through secretion of higher levels of toxic oxygen radicals. The latter has previously been reported in several studies. Neutrophils from diabetic cats were observed to secrete more toxic oxygen radicals when activated by phorbol myristate acetate compared to neutrophils from healthy cats, and intraperitoneal macrophages from alloxan-induced diabetic mice produced increased.