Background. Ischemia-reperfusion (I/R) injury is a complex process involving the generation and release of inflammatory cytokines, accumulation and infiltration of neutrophils and macrophages that may disturb the microcirculatory hemodynamics, thus damaging the skeletal muscle flap. Nonetheless, ischemic preconditioning (IPC) is known to produce immediate tolerance to subsequent prolonged I/R insults, although its underlying mechanism remains largely unknown. Our study investigated the role of IkB-a-NF-kB-TNF- a (tumor necrosis factor-a) pathway in IPC¢s ability to ameliorate I/R-induced microcirculatory disturbances in cremaster muscle flaps. Methods. Male Sprague Dawley rats were randomized (n=8 per group) into three groups: sham-operated control group, I/R group (4 hours of pudic epigastric artery ischemia followed by 2 hours of reperfusion), and IPC + I/R group (three cycles of 10 min ischemia followed by 10 min reperfusion before I/R). Intravital microscopy was used to observe leukocyte/endothelial cell interactions and quantify functional capillaries in cremaster muscles. Biochemical tests were implemented at the end of reperfusion periods. TNF-a protein level and IkB-a protein phosphorylation were determined by western blotting. Nuclear translocation of the transcription factor, NFkB, was examined via immunohistochemical analysis. Results. I/R markedly increased the number of rolling, adhering, and migrating leukocytes (Figure 1). It was also observed that I/R significantly increased the TNF-a expressions in these injured tissues (Figure 2). On the other hand, ischemic preconditioning prevented the I/R-induced increases in leukocyte rolling, adhesion, and migration (Figure 1). More over, TNF-a protein production and its mRNA expression were downregulated in the IPC group (Figure 2). Finally, I/R-induced IkB-a phosphorylation and NF-kB (p65) nucleus translocation were both suppressed by ischemic preconditioning. Conclusion. These results indicated that IPC attenuated NFkB activation and subsequently reduced TNF-a expression, which resulted in the amelioration of microcirculatory disturbances in I/R-injured cremaster muscles.