PURPOSE: To characterize the histological changes that occur after conductive keratoplasty (CK) using a rabbit model. SETTING: LSU Eye Center and Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, School of Medicine, New Orleans, Louisiana, USA. METHODS: Conductive keratoplasty was performed on 24 eyes of 12 New Zealand albino rabbits. In each eye, 24 spots were placed in a cross-corneal manner using 3 optical zones at 6.0, 7.0, and 8.0 mm. Eyes were assessed with corneal topography weekly. Rabbits were humanely killed 2,4, 6, and 8 weeks postoperatively. The eyes were then enucleated and processed for histopathology and immunohistochemical analysis. RESULTS: All eyes showed an initial mean steepening of the corneal curvature of 2.24 diopters (D) 2 weeks postoperatively. Corneal topography revealed a 26%, 36%, and 39% regression of the refractive results at 4, 6, and 8 weeks, respectively. Immunohistochemical analysis demonstrated keratocyte apoptosis, myofibroblast appearance, and upregulation of chondroitin sulfate, MMP-1, and Collagen III in the area surrounding the tip in each spot. CONCLUSION: The histological changes that occur after CK may be responsible for the well-established regression of its refractive effect. A better understanding of the wound-healing response after CK is necessary to improve the long-term stability of the procedure.