Prostaglandin (PG) D_2 is one of unsaturated fatty acids with 20 carbon atoms, which is synthesized by PGD synthase (PGDS) in the brain. PGD_2 has been identified to be a sleep-inducing substance that becomes bound to the DP receptor (DPR) exclusively localized on the surface of the basal forebrain, leading to an increase in extracellular adenosine levels there. Through A_ 2A receptors (A_ 2A R), the adenosine activates neurons in the ventrolateral preoptic area (VLPO), a putative sleep center, and inhibits neurons in the histaminergic tuberomammillary nucleus (TMN), a putative wake center, via GABA to induce sleep. Studying the effect and the molecular mechanisms of sleep-induced by PGD_2 would be helpful in the development of novel sleeping drugs for more rational treatment of sleep disorders.