Weibel-Palade bodies (WPB) are specialized cigar-shaped secretory organelles in endothelial cells, which contain a variety of biologically active molecules. These contents can be released rapidly by stimulation and involved in hemostasis, inflammation and angiogenesis. The main component of WPB is von Willebrand factor (vWF), whose expression and tubulation are necessary for the formation of the unique rod-like WPBs. Different molecules such as vWF, P-selectin, CD63, Rab27A and Rab3D are recruited into WPB mediated by the AP-1, AP-3 or other transport machinery. The underlying mechanism of the formation of WPB remains further investigation, which will gain insights into its function. The molecular mechanism of WPB formation and its function were discussed in this review.