We investigated the effect of a heat-shock protein co-inducer, arimoclomol (CytRx, LA, CA), on hypoxia-adaptive responses using a rat model of simulated altitude exposure (hypobaric hypoxia).Cognitive function was measured using a T-maze and an object recognition test.Motor function was measured using an inclined-screen test and an adhesion removal test. Immunohistochemical analyses were assessed in brain for heat-shock protein 70 (HSP 70), intercellular adhesion molecule 1 (ICAM- 1) and apoptosis (TUNEL staining). Results show that both cognitive and motor performances were improved in rats treated with arimoclomol during hypoxic exposure; the hypoxia-induced expression of HSP70 and ICAM-1, and TUNEL-positive cells were reduced in brain with the treatment.Our data suggest that the arimoclomol treatment reduces the hypoxia-induced stress in brain tissue, and also improves the behavioral performance in rats during hypoxic adaptation.