During mouse pregnancy placental lactogens stimulate prolactin receptors on pancreatic islet beta cells to induce expression of the tryptophan hydroxylase , resulting in the synthesis and secretion of serotonin. Presently, the functional relevance of this phenomenon is unclear. One hypothesis is that serotonin-induced activation of 5-HT receptors on beta cells stimulates beta cell proliferation during pregnancy. We tested this hypothesis via three different mouse models: (i) total KO mice, (ii) 129P2/OlaHsd mice, which are incompetent to upregulate islet during pregnancy, whereas is normally expressed in the intestine, mammary glands, and placenta, and (iii) -deficient mice. We observed normal pregnancy-induced levels of beta cell proliferation in total KO mice, 129P2/OlaHsd mice, and in mice. The three studied mouse models indicate that islet serotonin production and its signaling via 5-HT receptors are not required for the wave of beta cell proliferation that occurs during normal mouse pregnancy.