To compare the wound-healing process in the rabbit cornea after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) with the same refractive correction. Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. Adult albino rabbits (N = 24) were used. One eye of each animal had PRK or LASIK with the same refractive correction. Each animal was killed after an interval of up to 6 months. The expression pattern of corneal stromal injury-related molecules with the 2 treatments were compared. Paraffin sections of the cornea were processed immunohistochemically for alpha-smooth muscle actin (alpha-SMA), collagen type IV [alpha1(IV)](2),alpha2(IV), and heat shock protein (HSP) 47 as well as other HSPs. Sections were also examined after hematoxylin and eosin or periodic acid-Schiff staining. Hematoxylin and eosin staining showed the central epithelium to be thick in PRK-treated corneas. The thick epithelium was restricted to the area around the corneal flap edge adhesion in LASIK-treated corneas at 3 months. Periodic acid-Schiff staining showed an absence of or interruption in the epithelial basement membrane in PRK-treated corneas for up to 6 months. Heat shock protein 47 was detected in keratocytes on day 3 but not after that in PRK-treated corneas. There was no difference in the expression of other HSPs. Alpha-smooth muscle actin was expressed in keratocytes repopulated in the central anterior cornea of PRK-treated corneas at 28 days. Keratocytes with immunoreactivity for these 2 proteins were not seen in LASIK-treated corneas. Collagen IV [alpha1(IV)](2),alpha2(IV) was not detected in either group of corneas. The central epithelium became transiently thicker in PRK-treated corneas. Keratocyte responses to laser stromal ablation were more marked in corneas treated with PRK than in those treated with LASIK.