Abstract: The aim of this study is to detect the changes induced by chloroquine administration on the retina of rat using immunohistochemical and ultrastructural methods. Thirty-two male adult albino rats were used, divided into four groups (n = 8 each): 1, 2, 3 and 4, further subdivided into control (n = 2) and experimental (n = 6) subgroups. The experimental subgroups received chloroquine for one, two, three and four months, respectively. The eye balls were processed for light microscopic, immunohistochemical and ultrastructural evaluation, followed by morphometric assessment and statistical analysis. Examination of haematoxylin and eosin stained sections showed significant progressive thinning of Outer Reticular Layer (ORL) and Inner Nuclear Layer (INL) associated with decreased Ganglion Cell (GC) count. Positive Amyloid Precursor Protein (APP) immunostaining was first noticed in the GCs. Later, it was observed in the INL as well. Ultrastructural examination revealed cytoplasmic electron-dense membranous inclusion bodies in the ganglion, horizontal, amacrine and bipolar cells. The photoreceptors were involved on prolonged duration of administration.