Electrical stimulation has been shown to have neuroprotective effects on ganglion cells and photoreceptors in axotomized and dystrophic retinas from Royal College of Surgeons (RCS) rats. This study determined whether electrical stimulation also has a neuroprotective effect on cells in the inner nuclear layer (INL) of retinas. We cultivated retinas from adult RCS rats on microelectrode arrays and stimulated them continuously with 20 Hz for up to 5 days. Afterwards, we subjected them to quantitative immunohistochemical analysis. Using TUNEL assay we found that transretinal electrical stimulation (TRES) with charge densities within the range of 100-500 microC/cm2 reduced apoptosis of neurons in the INL of degenerated retinas from RCS -/- rats by 20% after 1 day of continuous stimulation. Antibody staining (OX-42, ED1) revealed a reduced activation of migroglial cells in RCS -/- and congenic control (RCS +/+) rat retinas by up to 50% after 1 day of stimulation. The effect of electrical stimulation on apoptosis and reduced activation of microglial cells was closely correlated with the strength and duration of the stimulation. The neuroprotective effect of TRES on neuronal cells in the INL of degenerated RCS rat retinas supports the idea that electrical stimulation may be a therapeutic option to delay the progression of retinal degeneration in patients suffering from retinitis pigmentosa.