Objective: Chronic hypoxia stimulates the development of pulmonary hypertension and remodeling by inducing marked changes in gene expression. However, the regulatory effect of chronic hypoxia on microRNA (miR) expression in the lung has not yet been investigated. The purpose of this study was to determine which miRs are regulated by chronic hypoxia in the mouse lung and to determine their functional significance. Methods: We compared the expression of miRs in mouse lung after 3 weeks normoxia versus hypoxia (10% O₂) treatment by Micro array hybridisation, and analysed the functional significance of these changes in mouse pulmonary vascular smooth muscle cells (PSMC). Results: Of the miRs regulated by hypoxia, the most significant decrease observed in the micro array was in miR- 223, a response verified by RT-qPCR. One target of miR-223 is the insulin-like growth factor 1 receptor (IGF1R) and we were able to demonstrate the binding of miR-223 to the wild-type 3'UTR of IGF1R, but not to a 3'UTR in which the potential binding site was mutated. We found that the expression of IGF1R was decreased following introduction of pre-mir-223 PMSC by 50%, an effect that correlated with the observed increase in IGF1R mRNA and protein levels in lungs from hypoxic mice. Correspondingly, pre- mir-223 attenuated IGF1-induced signaling in PSMC (Akt phosphorylation, migration and proliferation). Conclusion: The expression of miRs in the lung is modulated by chronic hypoxia and miR-223 may contribute to the development of pulmonary hypertension and vascular remodeling, by down-regulating IGF1R.