Objective: To explore the therapeutic effect and mechanism of methyl ophiopogonanone A(MOA) on dry eye disease(DED) rats. Methods: Male BALB/c mice(7~8 weeks old, weight 18-22 g) were randomly divided into 5 groups(n=12): control group,DED group, DED+10MOA group, DED+20MOA group and DED+40MOA group. Except the mice in control group, mice in other groups were given benzalkonium chloride solution with a mass concentration of 0.2% in both eyes to induce DED model mice, once a day for 6 weeks. After modeling, mice in the control group and DED group were intraperitoneally injected with 0.5 m L of 1% dimethyl sulfoxide solution, and mice in DED+10MOA group, DED+20MOA group and DED+40MOA group were intraperitoneally injected with0.5 m L 10, 20 and 40 mg/kg/d MOA, once a day for 28 days. After treatment, the tear secretion and corneal fluorescein sodium staining grade of mice in each group were detected, and corneal hematoxylin and eosin(HE) staining, conjunctival periodic acid-Schiff(PAS)staining and corneal TUNEL staining were performed. The expression level of corneal K10 protein was detected by Western blot. The levels of corneal oxidative stress indicators malondialdehyde(MDA) and superoxide dismutase(SOD) were detected. The m RNA levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), Bcl2-associated X(Bax) and B-cell lymphoma-2(Bcl-2)in cornea were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Results: Compared with control group, the tear secretion in DED group decreased(P<0.05), the grading of corneal fluorescein sodium staining increased(P<0.05),corneal lesions appeared, the number of conjunctival goblet cells decreased(P<0.05), corneal Bcl-2 m RNA relative expression level and SOD level decreased(P<0.05), corneal TUNEL positive rate, Bax m RNA relative expression level, K10 protein relative expression level,MDA, TNF-α, IL-1β and IL-6 levels increased(P<0.05). Compared with DED group, the tear secretion in DED+10MOA group,DED+20MOA group and DED+40MOA group increased(P<0.05), the grading of corneal fluorescein sodium staining decreased(P<0.05), the corneal lesions were alleviated, the number of conjunctival goblet cells increased(P<0.05). The positive rate of TUNEL, Bax m RNA, relative expression level of K10 protein, MDA, TNF-α, IL-1β and IL-6 levels decreased(P<0.05), while the relative expression level of Bcl-2 m RNA and SOD level increased(P<0.05). Conclusions: Methylophiopogonanone A effectively alleviates the symptoms and ocular surface lesions in mice with dry eye disease, and its mechanism may be related to the inhibition of goblet cell apoptosis,oxidative stress, and inflammation. [ABSTRACT FROM AUTHOR]