Inflammatory processes in lung alveoli, such as in pneumonia, acute respiratory distress syndrome, hyperoxia, ischemia-reperfusion, sepsis, COPD, cause the release of pro-inflammatory factors and reactive oxygen species from activated macrophages or pulmonary epithelial and endothelial cells. They damage the lungs and initiate inflammation causing dysfunction of the alveolar barrier and edema. Midkine is one of the molecules playing a significant role in the control of inflammatory processes. It promotes cell adhesion, migration, proliferation and survival. The signaling pathways mediating the effects of midkine in the lung tissue are only partially understood. The receptor mediating midkine responses is not well defined. Receptor tyrosine phosphatase cell-surface proteoglycan PTPzeta/RPTPbeta, low density lipoprotein receptor related protein and anaplastic lymphoma kinase (ALK), have been described to mediate the mitogenic activity of midkine. A heparin-independent high affinity binding site (p200+/MKR) causes midkine-dependent, heparin-independent phosphorylation and activation of the JAK/STAT pathway. Midkine interacts with HIF-1a- and hypoxia-dependent processes. LPS induced midkine secretion in monocytic cells depends on KATP channel and protein kinase C activation. In midkine deficient mice leukocyte infiltration into the blood vessels and kidney after ischemic injury is suppressed. However, the signaling pathways mediating the effects of midkine and mechanisms of action are only poorly understood. Protein kinase C, MAP kinase and G protein activation, as well as PTP, Erk1 and 2 and PI3-kinase are involved midkine induced migration of these cells. In this section signalling pathways take part in midkine related immune cell functions in normoxia and hypoxia will be discussed.