Recent data (Rivolta et al, 2011) demonstrated that lungs exposed to chronic hypoxia present regional adaptive differences. Some regions maintained the interstitial architecture of a good diffusor, some others developed focal edema. We hypothesize that local responses are consequence of pre-existing tissue features favouring fluid extravasation and remodelling. Based on this hypothesis, we analysed the expression of selected mediators potentially involved in the control of microvascular permeability in different lungs regions of normoxic rats. KGF (Keratinocyte Growth Factor), a controller of the matrix deposition, and Matrix Metalloproteinases (MMP) 2 are greatly expressed in the left lobes (58% and 14% more, respectively), with a predominance in the peripheral region of the upper one for KGF, and MMP2 prevailed in both the upper lobes. Conversely MMP17 expression is 13% higher in the right lung. Caveolin-1 exhibits a 17% increase in central areas respect to periphery, while PGC-1alpha, a strong O2 sensor and activator of mitochondrial biogenesis, is preferentially expressed in the periphery with a slight difference between left and right lung. We found that the proteins studied are less expressed in the right lower lobe which is the largest, most perfused and more exposed to the risk of pulmonary edema in conditions of increased microvascular permeability. We propose that this background may act and account for a differential response of the lung to the hypoxic insult.