Provided herein are macrophages engineered for treating fibrosis and ameliorating the effects of fibrotic lesions in various organs and tissues. Certain embodiments are directed to genetically-engineered macrophages capable of treating fibrosis or reducing fibrotic lesions. In certain aspects macrophages can be genetically-engineered to (1) target extracelluar matrix (ECM) or components thereof, (2) enhance degradation of ECM, or (3) target ECM and enhance degradation of ECM. Further provided is a cellular therapy product comprising a genetically-engineered macrophage comprising at least one of a recombinant targeting protein and a recombinant catalytic enzyme. Further provided is a method of treating an individual for fibrosis comprising administering the cellular therapy product.