Platelet-derived growth factor (PDGF)-A, which only signals through PDGF-receptor-alpha (PDGFRα) is required for secondary alveolar septal formation. Although PDGFRα distinguishes mesenchymal progenitor cells during the saccular stage, PDGFRα-expressing alveolar cells persist through adulthood. PDGF-A sustains proliferation, limits apoptosis, and maintains alpha-smooth muscle actin (αSMA) containing alveolar cells, which congregate at the alveolar entry ring at postnatal day (P)12. PDGFRα-expressing, αSMA-containing, alveolar cells re-distribute in the elongating septum, suggesting that they migrate to the alveolar entry rings where mechanical tension is higher. We hypothesized that PDGFRα and Ras-related C3 botulinum toxin substrate 1(Rac1) are required for mechanosensitive myofibroblast migration. Spreading of PDGFRα-deficient lung fibroblasts was insensitive to increased rigidity, and their migration was not reduced by Rac1-guanine exchange factor (GEF)-inhibition. PDGFRα-expressing fibroblasts migrated towards stiffer regions within 2-dimensional substrates by increasing migrational persistence (durotaxis). Using a Förster resonance energy transfer (FRET) biosensor for Rac1-GTP, we observed that PDGFRα was required for fibroblast Rac1-responsiveness to stiffness within a 3-dimensional collagen substrate, which by itself increased Rac1-FRET. Rho-GTPase stabilized whereas Rac1-GTPase increased the turnover of focal adhesions. Under conditions which increased Rac1-GTP, PDGFRα signaled through both phosphoinositide-3-kiase (PIK) or Src to engage the Rac1 guanine-exchange factors (GEF)s dedicator of cytokinesis-1 (Dock180) and p21-activated-kinase interacting exchange factor-β (βPIX). In cooperation with collagen fibers, these signaling pathways may guide fibroblasts toward the more rigid alveolar entry ring during secondary septation. Because emphysema and interstitial fibrosis disrupt the parenchymal mechanical continuum, understanding how mechanical factors regulate fibroblast migration could elicit strategies for alveolar repair and regeneration.