The extracellular niche is a key regulator of tissue morphogenesis and repair, however, its composition is currently not well characterized. Quantitative mass spectrometry resolved the dynamics of 8366 proteins from total tissue and bronchioalveolar lavage fluid in the consecutive phases of repair upon bleomycin induced lung injury. Joint analysis of proteome and transcriptome revealed posttranscriptional events during tissue remodeling. We developed a quantitative detergent solubility profiling method (QDSP), which enabled comprehensive characterization of the extracellular matrix and its interactions with secreted proteins, and showed the drastically altered association of morphogens, such as basement membrane netrins, to the insoluble matrix upon injury. We discovered several ECM proteins, including Emilin-2 and Collagen-XXVIII, as constituents of the provisional repair matrix. Our space and time resolved proteomics identified a host of tissue repair factor candidates with potential to promote the early events of progenitor cell mobilization or late events of repair pathways including the resolution of fibrosis.