Fibroblasts have a central role in the maintenance of tissue homeostasis and repair after injury. Currently, there are no tractable, cost-effective model systems for studying the biology of human fibroblasts in vivo. Here we demonstrate that primary human fibroblasts survive transplantation into zebrafish embryos. Transplanted cells migrate and proliferate, but do not integrate into host tissues. We used this system to study the intrinsic motility of lung fibroblasts from a prototype fibrotic lung disease, idiopathic pulmonary fibrosis (IPF). IPF fibroblasts displayed a significantly higher level of motility than did fibroblasts from nonfibrotic lungs. This is the first in vivo examination of primary human lung fibroblast motility in health and disease using zebrafish models.