OBJECTIVE: In this study, we investigate the role of adiponectin in the interaction between leukocytes and endothelium in the secondary inflammatory reaction of cerebral ischemia. METHODS: Adiponectin knock-out mice group (APN-KO) (n = 8) and wild-type mice group (WT) (n = 8) were prepared. Each group was sub-divided into 2 groups by reperfusion time. One-hour middle cerebral artery occlusion and reperfusion were induced using the intraluminal filament technique. At 6 and 12 hours after the occlusion, the mice were placed on a stereotactic frame to perform craniotomy in the left parietal area. After craniotomy, a straight pial venule was selected as a target vessel. With the fluorescence intravital microscope, the number of rolling leukocytes and leukocytes that adhered to endothelium were counted and documented at 6 and 12 hours after the reperfusion. RESULTS: At 6 and 12 hours after the reperfusion, more rolling leukocyte and leukocyte adhesion were observed in the APN-KO mice than in the WT mice. The difference in leukocyte numbers between the APN-KO and WT mice was found to be statistically significant (p = 0.029) by Mann-Whitney U-test. CONCLUSION: We found that adiponectin inhibits the interaction between the endothelium and leukocytes in cerebral ischemia-reperfusion. Therefore adiponectin might prevent the secondary insult caused by the inflammation reaction.