AIM: To determine the disparate expression of autophagy in the Aspergillus fumigatus (A. fumigatus) keratitis between susceptible C57BL/6 mice and resistant BALB/c mice. METHODS: C57BL/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 C57BL/6 and BALB/c mice at 1, 3 and 5d. 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 C57BL/6 and BALB/c mice at 1, 3 and 5d 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 C57BL/6 mice versus BALB/c mice at 1, 3 and 5d p.i. H&E staining showed that the number of inflammatory cells was larger and the severity of ulcer was higher in C57BL/6 mice than in BALB/c mice after stimulation with A. fumigatus. Higher expression of LAMP-1, Beclin-1, and LC3 was shown in C57BL/6 mice corneas than in BALB/c mice corneas at 1, 3 and 5d p.i., while the expression of p62 was lower in C57BL/6 mice. The fluorescence of LC3 was significantly increased in corneas of C57BL/6 mice compared with BALB/c mice after A. fumigatus infection. CONCLUSION: The expression of autophagy is higher in corneas of C57BL/6 mice than in BALB/c mice after A. fumigatus infection. Autophagy may be positively correlated with keratitis severity and pathological changes.