Citicoline is an essential endogenous intermediate in the biosynthesis of phosphatidylcholine, which acts as a therapeutic agent in models of central nervous system injury and neurodegenerative diseases. The present study investigated the effects of citicoline on extracellular-signal-regulated kinase 1/2 (ERK1/2) expression in the rat retina after kainic acid (KA) treatment. KA (6 nmol) was injected into the vitreous of the rat eyes. The animals were then injected intraperitoneally with citicoline (500 mg/kg) twice daily after the KA injection. The neuroprotective effects of citicoline were estimated by evaluating temporal changes in ERK1/2 using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL), immunoblotting and immunohistochemical techniques. The expression of phosphorylated ERK1/2 was slightly decreased after 6 h, and significantly reduced after 12 h, in the rats receiving the KA injection plus citicoline treatment. Our results demonstrated that citicoline decreased the activation of ERK1/2 due to the KA treatment, suggesting that it exerts its neuroprotective activity by reducing the concentrations of proteins involved in apoptosis.