Phrynocephalus vlangalii is a species of lizard endemic in China, which lives on Qinghai-Tibet Plateau ranging from 2000 to 4600 m above sea level. In this study, P. vlangalii were collected from low altitude (2750 m) and high altitude (4564 m). The lizards from low altitude were acclimatized in simulated hypoxic chamber (equivalent to 4600 m) for 7, 15, and 30 days. The hematological parameters, heart weight, myocardial capillary density, and myocardial enzyme activities were examined. The results showed that acclimatization to hypoxia significantly increased hemoglobin concentration ([Hb]), hematocrit (Hct), heart weight (HW), heart weight to body mass (HW/BM), lactate dehydrogenase (LDH) activity, but markedly decreased mean corpuscular hemoglobin concentration (MCHC) and succinate dehydrogenase (SDH) activity. Red blood cell (RBC) count, body mass (BM), myocardial capillary density did not change markedly during hypoxic acclimatization. On the other hand, [Hb], Hct, MCHC, HW/BM, myocardium capillary density, and SDH activity of P. vlangalii from high altitude were remarkably higher than those from low-altitude; however, LDH activity of high-altitude P. vlangalii was lower than that of low-altitude lizards. There was no significant difference in HW or BM between populations of high-altitude and low-altitude. Based on the present data, we suggest that P. vlangalii has special anatomical, physiological, and biochemical accommodate mechanisms to live in hypoxic environment, and the regulative mechanisms are different between hypoxic acclimatization and adaptation. J. Exp. Zool. 319A:117–123, 2013. © 2013 Wiley Periodicals, Inc.