Objective: We aimed to investigate the effects of tacrolimus on plasma endothelin-1, melatonin and brain Hsp-70 levels in experimental ischemic stroke in this study.Material and Methods: Twenty-one male Wistar-Albino rats randomly divided into three groups which included seven rats. Animals in group 2 and group 3 were anesthetized and bilateral common carotid arteries were clamped with aneurysm clips for 10 minutes. Animals in group 1 were not clamped and were not given any treatment. Rats in group 2 were received 1 ml saline and in group 3 were received 1 mg/kg tacrolimus intraperitoneally. Injections were applied 1st hour before ischemia and at 6th, 24th, 48th and 72nd hours post ischemia. All the animals were decapitated on the 4th day and plasmas were obtained and brains were excised. Plasma endothelin-1 and melatonin levels were measured. Brain Hsp-70 immunostaining and neuron cell death were scored semiquantitatively.Results: The plasma endothelin-1 levels in group 3 were higher than group 2 and group 1, but were similar in group 1 and group 2. In group 1 plasma melatonin levels were lesser than group 2 and group 3. In group 2 plasma melatonin levels were higher than group 3. The mean neuron death in group 3 was lesser than in group 2. The mean Hsp-70 immunostaining intensity in group 2 was greater than group 3 and group 1. In group 1 the mean Hsp-70 immünostaining intensity was lesser than group 3. Conclusions: Tacrolimus administration in ischemic stroke reduces plasma melatonin and brain Hsp-70 levels and increases plasma endothelin-1 levels and has neuroprotective effect.