Growing evidence supports the concept that human polymorphonuclear neutrophils (PMN) promote inflammation-mediated angiogenesis. Whereas neovascularization by sprouting angiogenesis is critical for wound healing and repair, the underlying molecular mechanisms are still not exactly defined. By means of oligonucleotide microarray technique, we identified midkine (MDK), a novel cytokine in human PMN freshly isolated from the circulation. This result was confirmed by reverse transcription and polymerase chain reaction (RT-PCR) technique at the mRNA level and by means of western blotting technique at the protein level. Stimulation of the PMN by the bacteria-derived tripeptide N-formyl-Met-Leu-Phe (fMLP, 100 nM) induced a 6-fold up-regulation of MDK protein expression within 6 h after stimulation when compared to unstimulated control. The biological relevance of these findings was studied in vivo by measuring sprouting angiogenesis in the chicken chorioallantoic membrane assay. Here, MDK (100 ng/ml) was found to induce a 2.6-fold increase of angiogenesis when compared to unstimulated control. This effect was similar to the response observed upon stimulation by vascular endothelial growth factor (100 ng/ml). Taken together, we identified the novel proangiogenic cytokine MDK in human PMN which may be involved in inflammation-mediated angiogenesis during wound healing and repair. Supported by DFG (WA 1048/1-2).