Lymphangioleiomyomatosis (LAM) is characterized by a proliferation of LAM cells, a smooth-muscle-like cell type, in the lungs, lymph nodes, and other organs. Their proliferation induces LAM by producing vascular endothelial growth factors (VEGFs). These cells express VEGFs, and lymphatic endothelial cells in the lesions of LAM express VEGF-R3 and the receptors of VEGF-C and -D. Because the serum level of VEGF-D is elevated in patients with LAM, it may serve as a diagnostic marker of LAM. In the present study, we measured the serum levels of VEGF-C, VEGF-D, and VEGF-R3 in 6 patients with LAM and compared these levels with those in patients having chronic obstructive pulmonary disease and with healthy volunteers. The serum levels of VEGF-D were significantly higher in patients with LAM than in healthy volunteers, and they were negatively correlated with FEV_1.0% and %DL_CO, but they were not significant. The serum levels of VEGF-R3 were higher in patients with LAM than in the other groups, but the difference was insignificant. We suggest that serum VEGF-D is a useful marker for the diagnosis of LAM and the evaluation of its severity.