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AIM: To determine the disparate expression of autophagy in the Aspergillus fumigatus(A. fumigatus) keratitis between susceptible C57 BL/6 mice and resistant BALB/c mice.METHODS: C57 BL/6 and BALB/c mice were used to establish fungal keratitis models. Disease severity and inflammatory response were observed by slit lamp microscopy in A. fumigatus-infected corneas of C57 BL/6 and BALB/c mice at 1, 3 and 5 d. Hematoxylin-eosin(H&E) staining was used to detect pathological changes of corneas. The expression of autophagy-related proteins Beclin-1, LC3, SQSTM1/p62, and LAMP-1 was assessed by Western blot in C57 BL/6 and BALB/c mice at 1, 3 and 5 d post infection(p.i.). Immunofluorescent staining was used to test the expression of LC3 in corneas after A. fumigatus infection.RESULTS: Keratitis severity was higher in C57 BL/6 mice versus BALB/c mice at 1, 3 and 5 d p.i. H&E staining showed that the number of inflammatory cells was larger and the severity of ulcer was higher in C57 BL/6 mice than in BALB/c mice after stimulation with A. fumigatus. Higher expression of LAMP-1, Beclin-1, and LC3 was shown in C57 BL/6 mice corneas than in BALB/c mice corneas at 1, 3 and 5 d p.i., while the expression of p62 was lower in C57 BL/6 mice. The fluorescence of LC3 was significantly increased in corneas of C57 BL/6 mice compared with BALB/c mice after A. fumigatus infection.CONCLUSION: The expression of autophagy is higher in corneas of C57 BL/6 mice than in BALB/c mice after A. fumigatus infection. Autophagy may be positively correlated with keratitis severity and pathological changes.