To investigate the expression of four subtypes of prostaglandin E2 E-prostanoid receptor (EP1-EP4) and the effects of EP3/EP4 on bladder dysfunction in a new neurogenic bladder model induced by experimental autoimmune encephalomyelitis (EAE), the mice model of EAE were induced using a previously established method and then bladder function in mice with different defined levels of neurological impairment were examined, including micturition frequencies and voiding weight. The bladders were then harvested for analysis of EP receptor expression by Western blot. The activities of agonists/antagonists of the EP3 and EP4 receptors as well as PGE2 were also evaluated at different stages of EAE. The results showed that the EAE mice developed profound bladder dysfunction characterized by significantly increased micturition and significantly decreased urine output per micturition. EAE-induced up-regulation of EP3 and EP4 receptors in the bladder was accompanied by bladder dysfunction. However, EAE had no significant effect on the EP1 and EP2 receptors. Moreover, PGE2 and the agonists/antagonists of EP3 and EP4 receptors significantly affected bladder dysfunction in EAE mice. Thus, we indicated that EAE mice are useful for investigating neurogenic bladder. In addition, the EP3 and EP4 receptors play a role in EAE-induced bladder dysfunction, providing us with a new target for treatment of neurogenic bladder.