The hyperpolarized 129Xe chemical shift saturation recovery (CSSR) method combined with mathematical models of gas uptake provides unique insights into lung microstructure and function. Here, we propose a generalization of the Patz model for assessing interstitial membrane permeability. We test the model’s potential for in-vivo determination of membrane permeability by fitting to CSSR data from healthy volunteers and pulmonary hypertension (PH) patients. The obtained permeabilities lie between those estimated for O2 and CO2 in healthy volunteers and tend to be lower in PH. The proposed model enables the non-invasive assessment of interstitial barrier permeability and shows potential as diagnostic tool.