Maintaining the integrity and transforming button-to-zipper junctions in lacteals are strongly connected with obesity, which could be regulated by intestinal flora and molecular signalings, such as vascular endothelial growth factor C-vascular endothelial growth receptor 3 (VEGFC-VEGFR3) signaling, Hippo signaling, Notch signaling, angiopoietin-TIE signaling, VEGF-A/VEGFR2 signaling, and PROX1. This manuscript reviews the molecular mechanism of development, integrity maintenance, and junction transformation in lacteal related to obesity. This evidence concerns the gene FLT4 and obesity due to melanocortin 4 receptor deficiency.