Late-onset reduction of muscarinic acetylcholine receptors (LORMAR) in the ischemic gerbil hippocampus begins as late as 7 days after a 5-min transient forebrain ischemia and reperfusion. We previously reported that LORMAR is prevented by postadministration of cyclosporin A. In the present study, we aim to elucidate whether the LORMAR can also be prevented by post-ischemic administration of the immunosuppressant FK506 (tacrolimus). We investigated changes in muscarinic acetylcholine receptor binding capacity and histological examination in the transient forebrain ischemic gerbil hippocampus and the effect of this agent on these changes. In the ischemic vehicle-treated group, muscarinic acetylcholine receptors significantly decreased in the hippocampus as the LORMAR with subsequent disruption of the pyramidal cells in the CA1 area. On the other hand, LORMAR is prevented by daily subcutaneous administration of low dose of FK506 (0.5 mg/kg/day) for 10 days after the ischemic insult, although delayed neuronal cell death was not prevented. Thus, we showed that the LORMAR is attenuated by post-administration of FK506.