Abstract: OBJECTIVE To observe the clinical effect of natamycin eye drops on fungal keratitis, and to discuss the mechanism of drug treatment so as to improve the clinical efficacy for patients with fungal keratitis. METHODS A total of 80 cases (80 eyes) of patients with fungal keratitis admitted from Jan. 2013 to Oct. 2015 were analyzed. Randomized controlled trials were conducted to divide them into control group and experiment group with 40 cases each. The control group received voriconazole eye drops, while the experimental group used natamycin of eye drops for topical treatment. The clinical effects of the two groups were compared. RESULTS The total effect rate of the experimental group was 95%, which was significantly higher than that of the control group (P<0.05); the relapse rate of the experiment group was 5%, which was significantly lower than the control group (P<0.05); the differences between two groups of patients with vision ≤0.1,0.1~0.3 and ≥0.3 were not significant; the cases of vision ≥0.3 in experimental group after treatment were significantly more than the control group (P<0.05); while visual acuity ≤0.1, 0.1~0.3 in experiment group were significantly less than the control group (P<0.05); the differences of eye scores between two groups of patients before difference treatments were not significant; the eye scores of the experimental group after treatment in 3 d, 7 d, 14 d, 28 d were significantly lower than those of the control group (P<0.05). CONCLUSION Natamycin eye drops have great effect and low incidence of adverse drug reactions on patients with fungal keratitis. They can improve eye vision so can be applied widely.