Abstract： Objective To observe the effects of Rhodiola on the rat retinal tissue morphology and the hypoxia-inducible factor (HIF)-1α at simulated hypoxia at different altitudes.Methods Forty-eight adult female Sprague Dawley rats were randomly divided into the Rhodiola Intervention group (intervention group) and the control group,each group had 24 rats.The intervention group rats were treated with intraperitoneal injection of 10 ml/kg of large plants Rhodiola solution,and the control group rats were injected with same volume of saline.One hour after the injection,six rats were randomly selected from both of the two groups and reared in the plateau environment simulation laboratory modules with the oxygen partial pressure of 17.4,14.6,11.3 and 7.4 kPa,which simulated the altitudes of 1500,3000,5000 and 8000 meters indoor respectively.Six hours later the rat eyeballs were harvested for paraffin sections and analyzed by hematoxylin and eosin staining,and immunohistochemical staining to observe the expression of HIF-1α and p53.Results In the control group,the rat retinal layers were edema and loose,the retinal thickness increased,the retinal structure was disorganized,the ganglion cells were swollen and degenerated,and some can observe the karyopyknosis,karyolysis and the reduced cells number.As the altitude increased,the pathological changes of retinal became more obvious.In the intervention group,the characteristics of rat retinal morphology were same with the control group,while the degree of morphology changes was lighter than the control group.HIF-1α and p53 expressed mainly in the ganglion cell layer and inner nuclear layer of rat retina in the control group.As altitude increased,the expression of HIF-1α and p53 were increased too,which was positive correlated (r=0.9846,P＜0.05).Compared with the control group,the rat retinal expression of HIF1α increased,while expression of p53 decreased in the intervention group,and the differences were statistically significant (P＜0.05).Conclusion Rhodiola can reduce the retinal tissue pathology damage caused by high altitude hypoxia,and its mechanism may be related to the increasing expression of HIF-1α and reducing expression of p53.