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Objective To study the protective effects of the total bakkenolides from P. tricholobus on high altitude hypoxia. Method Normobaric hypoxia model and acute hypobaric hypoxia model in mice, hypobaric hypoxia model in rats were established for this study. Survival time and survival rate of mice were recorded. The level of blood sugar and glycogen, adenosine triphosphate (ATP), lactic acid (LD), lactic dehydrogenase (LDH) were detected in different organs of rats. Results The total bakkenolides significantly prolonged the survival time of mice in normobaric hypoxia model and reduced the death rate of mice in acute hypobaric hypoxia model. The total bakkenolides suppressed blood sugar level in rats and increased the glycogen level in rat liver, skeletal muscle and myocardium. It also elevated the ATP content in rat brain, liver, skeletal muscle and myocardium. Meanwhile, the content of LD in plasma, skeletal muscle, myocardium and LDH level in myocardium were reduced. Conclusion The total bakkenolides from P. tricholobus have protective effect on normobaric hypoxia model and acute hypobaric hypoxia model in mice as well as hypobaric hypoxia model in rats. Its anti-hypoxia efficacy at high altitude may relate to the increased blood sugar, glycogen, and ATP level and reduced LD, LDH level in major organs. [ABSTRACT FROM AUTHOR]