OBJECTIVE： To observe the efficacy and safety of vitamin A acid combined with vitamin A， vitamin E， celecoxib in the treatment of oral leukoplakia. METHODS： 104 patients with oral leukoplakia were randomly divided into control group （52 cases） and observation group （52 cases）. Control group received 1 Vitamin A soft capsule， 3 times a day+1 Vitamin E soft capsule， 3 times a day+1 Celecoxib capsule， twice a day. Observation group additionally received 1 Vitamin A acid tablet， twice a day. 4-week was regarded as 1 treatment course， it lasted for 3 courses. Clinical efficacy， and leukoplakia number， maximum diameter of leukoplakia， immunoglobulin A （IgA）， IgM， IgG before and after treatment， and the incidence of adverse reactions in 2 groups were observed. RESULTS： The total effective rate in observation group was significantly higher than control group， the difference was statistically significant （P＜0.05）. Before treatment， there were no significant differences in leukoplakia number， maximum diameter of leukoplakia， immunoglobulin levels in 2 groups （P＞0.05）. After treatment， leukoplakia number， maximum diameter of leukoplakia，IgA and IgM in 2 groups were significantly lower than before， and observation group was lower than control group， IgG was significantly higher than before， and observation group was higher than control group， the differences were statistically significant （P＜0.05）. And there was no significant difference in the incidence of adverse reactions in 2 groups （P＞0.05）. CONCLUSIONS： Vitamin A acid combined with vitamin A，vitamin E， celecoxib shows obvious efficacy in the treatment of oral leukoplakia， it can effectively reduce clinical symptoms， improve immune function， with good safety.