Publisher Summary This chapter describes the proliferation and differentiation of retinal pigment epithelium (RPE) during development and regeneration. RPE is a pigmented monolayer of hexagonal cells of neural origin located between the neural retina and the choroid. It is one of the most important structures in the visual system because of the role it plays in the viability and function of the neural retina. The comparison of RPE development in three species (rats, chicks, and humans) showed that the pattern and schedule of RPE growth and differentiation causally related to cell proliferation are significantly different. The chapter discusses the proliferation of pigment epithelium cells in the amphibian retina and iris in the process of retinal and lens regeneration. The importance of analyzing the proliferative activity of pigmented epithelia of the amphibian eye is because of the amphibian's striking potential for the regeneration of the neural retina and lens. Cell proliferation is not only closely related to cell multiplication and the reduction of cell volume but is also essential for RPE melanotic differentiation and for transdifferentiation into other cell types.