Objectives: In this study the authors investigated effects of the ethanolic extract of Rhodjola Rosea(HKC) on fatigue and hypothalamic IEG expression in rat forced swimming(FS) model. Methods: Sprague-Dawley rats were administered HKC extract(25 mg/100g, p.o.) for 3 days prior to FS, some rats underwent 10 min FS and others exhaustive forced swimming(EFS). In addition, other rats were administered extract at different times after EFS over 3 consecutive days. Results: When HKC administered before 10 mins of FS, serum actate dehydrogenase(LDH) and creatine phosphokinase(CPK) activities were significantly lower than control group. When HKC administered prior to EFS, blood lactate was significantly lower versus control group. When HKC was administered after EFS, blood lactate(at 6 and 24 hours after EFS) were significantly lower and serum LDH, CPK activities(at 24 hours after EFS) were significantly lower versus control group. When HKC was administered after EFS, c-Fos positive neurons in hypothalamic periventricular area(PVA), medial part(mPVN) and anterior hypothalamic nucleus caudal part(AHC) were significantly lower at 24 hours after EFS than in control group. HSP-72 positive neuron numbers in hypothalamus were significantly lower at 24 hours after EFS than in control group. Finally, when HKC was administered prior to 10 mins FS, HIF-$1{alpha}$ expression in the gastrocnemius muscle was significantly increased. Conclusions: These results suggest that HKC extract has an anti-fatigue effect, and it reduces neuronal cell stress responses induced by physical stress by having a beneficial effect on lactate metabolism.