Activation of the immune system and progressive fibrosis are prominent features of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation. The main histologic findings in affected exocrine glands are marked fibrosis of the interstitium and prominent increase in the number of fibroblasts, accompanied by mild lymphocytic infiltration. Clinically, the severity of dry eye is correlated with the degree of fibrotic changes, rather than with the amount of lymphocytic infiltration, indicating that excessive extracellular matrix accumulation primarily contributes to the exocrine dysfunction. We have found that accumulated fibroblasts in the lacrimal gland of patients with cGVHD have a chimeric status. Thus, fibroblasts originating from circulating donor-derived precursors and recipient-derived fibroblasts by local epithelial mesenchymal transition may participate in the excessive fibrosis in patients with cGVHD by interacting with T cells. In this article, the immune response and pathogenic fibrosis in ocular cGVHD will be discussed. In addition, clinical findings of ocular complications after hematopoietic stem cell transplantation and currently available treatment will also be discussed.