We studied the protective effects of midkine, a growth factor produced by a retinoic acid responsive gene, on constant light-induced retinal damage in albino BALB/C adult mice. Two days before exposure to constant light, midkine was injected into the vitreous of the left eye and a phosphate buffer saline into the right eye (control eyes). After 7 days of constant light, control eyes exhibited shortening of the photoreceptor outer segments and decreased thickness of the outer nuclear layer, whereas in midkine-treated eyes photoreceptor cells were virtually intact. Although midkine-treated eyes also showed photoreceptor damage after longer light exposure of up to 21 days, the damage was significantly less than in control eyes. Measurement of the thickness of the outer nuclear layer showed the protective effect of intravitreous midkine on the constant light-induced retinal damage. These findings suggest that midkine is a potential agent for the prevention of photoreceptor degeneration.