Consistent with our findings with HMGB1 blockade resulting in impaired lymphangiogenesis, we found that TLR knockout mice had more severe lymphedema, decreased lymphatic transport, abnormal lymphatic structures, decreased number of lymphatic capillaries, increased collagen deposition and dermal fibrosis, and increased infiltration of T cells as compared with wild-type controls. This evidence concerns the gene HMGB1 and lymphedema.