Abstract: OBJECTIVE To explore establishmentand preliminary application of a rat model of orthostatic hypotension. METHODS The rat model of orthostatic hypotension was optimized from angle of tilt(30°, 45°, 75°, 90°)and tilt time(1 min or 2 min). The validity and reliability of the model were observed by administrated with prazosin(1.1-220 μg·kg^-1) and naphthalene (30-3 000 μg·kg^-1) RESULTS With the increase of angle, variation amplitude of rats’ blood pressure and heart rate all increased. The duration of position and the change of blood pressure and heart rate had no obvious correlation. Prazosin dose dependent strengthened orthostatic hypotension. Blood pressure and heart rate were obviously inhibited. Only 3 000 μg·kg^-1 naphthalene had inhibitory effect on blood pressure and heart rate. CONCLUSION 45°head-up tilt and 60 s is the optimum condition to establish a rat model of orthostatic hypotension; the results of administrating prazosin and naphthalene are consistent with the literature reports proving the validity and reliability of the model.