Objective: To investigate the cell proliferation rate of normal corneal epithelium with extended orthokeratology lens (OKL) wear in comparison with extended rigid gas-permeable (RGP) lens wear. Methods: Twenty-four rabbits were fitted unilaterally with either an OKL or an RGP lens, and the other eye was used as a control. They were injected with 5-bromo-2-deoxyuridine (BrdU) 24 h prior to being sacrificed. The rabbits were sacrificed at 1, 3, 7 and 14 days after lens fitting. The cornea from the superior limbus to the center was taken at 1.0-mm intervals. The BrdU-labeled cells were counted in medium power fields (×200) in each sample using light microscopy. Results: The number of BrdU-labeled cells in the RGP lens group initially increased, but the number decreased in the corneal center and superior limbus by 32 and 8%, respectively, after 14 days. There was no statistically significant change. However, the number of BrdU-labeled cells in the OKL group decreased after 3 days, and the number of BrdU-labeled cells was reduced in the center and superior limbus by 63 and 8%, respectively, after 14 days. The change in proliferation in the corneal center in the OKL-wearing rabbits was statistically significant compared to the control (p < 0.05). Conclusions: Wearing an OKL had a greater effect on the change of the proliferation pattern in the epithelium than wearing an RGP lens, which suggests that the OKL might be less physiologic than the RGP lens is.