Purpose. To compare Ganoderma spores lipid (GSL) and fish oil (FO) in inhibiting retinal photoreceptor cell lesions induced by N-methyl-N-nitrosourea (MNU) in rats. Methods. 120 rats were untreated (normal control, NC group) or treated with a single intraperitoneal injection of 40 mg/kg MNU (MNU group) then treated with GSL (GSL group) or FO (FO group). Eyes were obtained at 1, 3, 5, 7, and 10 days. Results. Light microscopy assay demonstrated that GSL and FO alleviated rat retinal photoreceptor cell damage (GSL and FO versus MNU group P < .001) similarly (GSL versus FO group P = .980). Electron microscopy confirmed that GSL and FO reversed damage to photoreceptor segments and photoreceptor cell nuclei. GSL-treated rats showed significantly elevated a-wave and b-wave amplitudes over MNU group (P < .05) but less than NC group (P < .05) and not significantly different from FO group (P > .05). Conclusion. GSL, like FO, alleviates rat retinal photoreceptor cell damage induced by MNU.