Abstract: Objective: In this study, the molecular weight of the polysaccharide from Dendrobium officinale was detected and its main influence factors were discussed.Method: The polysaccharide of the Dendrobium officinale was obtained through extraction and isolation process. And the purified polysaccharide fraction named WDOPA was obtained using DEAE cellulose and sephadex gel Sephacryl S-300 column. The HPGPC method was performed to determine its molecular weight. The processing method for the polysaccharide from Dendrobium officinale was heating and ultrasonic dealing. The influence factors such as heating temperature, heating time, ultrasonic power and duration time were investigated by single factor.Results: The molecular weight of WDOPA was 776054 u, RSD was within 10%.The heating temperature and time did not have significant effects on the molecular weight of the polysaccharide while the ultrasonic dealing had.As the ultrasonic power and duration time increased, the molecular weight of the polysaccharide decreased.Conclusion: This experimental method could be used for the detection of the molecular weight of the polysaccharide. Ultrasonic dealing would change the molecular weight of the polysaccharide from Dendrobium officinlae, this could be applied in produce polysaccharide with different molecular weight.