OBJECTIVE： To compare therapeutic efficacy and safety of dexamethasone with different administration routes in the treatment of chronic secretory otitis media. METHODS： A total of 150 patients with chronic secretory otitis media were randomly divided into control group （75 cases） and observation group （75 cases）. Control group was given Dexamethasone sodium phosphate injection 5 mg by auripuncture under endoscope. Observation group was given Dexamethasone sodium phosphate injection 5 mg via eustachian tube under endoscope. Both groups were given relevant medicine every 2 days， for 3 times in total. Clinical efficacies of 2 groups were observed as well as bone conduction threshold under 1， 2， 4， 8 kHz， the levels of water channel protein 1 and water channel protein 4， recurrence， the occurrence of tympanic cavity effusion before and after treatment. The occurrence of ADR was recorded. RESULTS： The total response rate of observation group （93.33％） was significantly higher than that of control group（80.00％）； recurrence rate and the incidence of tympanic cavity effusion of observation group were significantly lower than those of control group， with statistical significance （P＜0.05）. Before treatment， there was no statistical significance in bone conduction threshold， the levels of water channel protein 1 and water channel protein 4 between 2 groups （P＞0.05）. After treatment， the levels of bone conduction threshold in 2 groups were significantly lower than before； the observation group was significantly lower than the control group. The levels of water channel protein 1 and water channel protein 4 in 2 groups were significantly higher than before； the observation group was significantly higher than control group， with statistical significance （P＜0.05）. There was no statistical significance in the incidence of ADR between 2 groups（P＞0.05）. CONCLUSIONS： The administration of dexamethasone via eustachian tube under endoscope is significantly better than auripuncture in terms of therapeutic efficacy for chronic secretory otitis media， relieving clinical symptom， improving bone conduction threshold， up-regulating water channel protein level， reducing the risk of recurrence and tympanic cavity effusion. The two routes of adimistration have similar safety.