Recent studies demonstrate that sustained hypoxia induces the robust accumulation of leukocytes and mesenchymal progenitor cells in pulmonary arteries (PA). Since the factors orchestrating hypoxia-induced vascular inflammation are not well defined, the goal of this study was to identify mediators potentially responsible for recruitment to and retention and differentiation of circulating cells within the hypoxic PA. We analyzed mRNA expression of 44 different chemokine/chemokine receptor, cytokine, adhesion, and growth and differentiation genes in PAs obtained via laser capture microdissection, in adjacent lung parenchyma and in systemic arteries by RT-PCR at several time-points of hypoxic exposure (1-, 7-, 28 days) in Wistar-Kyoto rats. Analysis of inflammatory cell accumulation and protein expression of selected genes was concomitantly assessed by immunochemistry. We found that hypoxia induced progressive accumulation of monocytes and dendritic cells in the vessel wall with few T-cells and no B-cells or neutrophils. Upregulation of SDF-1, VEGF, GRO-, C5, ICAM-1, OPN, TGF-, preceded mononuclear cell influx. With time, a more complex pattern of gene expression developed with persistent upregulation of adhesion molecules (ICAM-1, VCAM-1, OPN) and monocyte/fibrocyte growth and differentiation factors (TGF-, ET-1, 5-LO). On return to normoxia, expression of many genes (including SDF-1, MCP-1, C5, ICAM-1, TGF-) rapidly returned to control levels; changes which preceded the disappearance of monocytes and reversal of vascular remodeling. In conclusion, sustained hypoxia leads to the development of a complex, PA-specific, pro-inflammatory microenvironment, capable of promoting recruitment, retention and differentiation of circulating monocytic cell populations that contribute to vascular remodeling.