Background: Panax notoginseng (PN) is one of the most commonly used Chinese herbal drugs. Panax notoginseng saponins (PNS) is the main effective components of PN. However, the anti-fatigue effect of PNS in plateau-condition is unknown. Objective: Explore the anti-fatigue effects of PNS in mice living under simulation plateau-condition. Materials and Methods: Hundred male Kunming mice were randomly divided into five groups (n=20): one normoxia control group (NCG), one hypoxia control group (HCG), and three PNS groups in low dosage (0.42 g/kg), mid dosage (1.11 g/kg), and high dosage (11.53 g/kg). HCG and PNS groups were fed at a simulated elevation of 5 km. NCG and HCG were intragastric administrated with distilled water. After continuous administration for 10 days, the exhaustive swimming time, glycogen contents in liver, blood lactic acid (BLA), and blood glucose were determined. Results: Exposure of the mice to simulation plateau-condition with 5 km altitude for 10 days caused significant decrease of exercise tolerance compared to normoxia environment. The swimming time and glycogen contents in liver were significantly increased at all tested concentration (0.42, 1.11, and 11.53 g/kg). The area under the BLA curve was significantly decreased at the concentration of 0.42 g/ kg. The blood glucose of resting and 0 minutes after swimming were significantly increased by 29.31% and 15.51% (P<0.05) at a concentration of 11.53 g/kg compared to their own control groups, respectively. Conclusion: These results indicate that PNS could postpone the appearance of fatigue and accelerate the restoration of fatigue in plateau environment, especially in low dosage (0.42 g/kg) case.