Objective To observe the effect of persistent flickering stimulus on the structure and function of retina in guinea pigs during a developmentally sensitive period.Methods Twenty-four two- week-old guinea pigs were randomly divided into flicker light (FL) group and control group, with 12 guinea pigs in each group. Animals in FL group were raised under 500 Lux illumination with a duty diurnal cycle of 50% at a flash rate of 0.5 Hz. Animals in control group were reared under steady 500 Lux illumination. Light emitting diode (LED) lamps were used for lighting under a 12-hour light/12-hour dark cycle. After the collection of fundus photographs and electroretinograms recorded at week 12, eyeballs were taken out, three dimensions were measured, and histopathological changes were examined.Results Compared to control group, tessellated fundus in FL group appeared more prevalent; implicit time of ldquo;ardquo; waves were prolonged in electroretinogram; the eyeballs were increased in horizontal, vertical, axial dimensions by (0.89plusmn;0.30), (0.69plusmn;0.20) and (0.96plusmn;0.30) mm respectively, the differences between two groups were statistically significant (t=12.7,11.9,15.8;P＜0.05). The gap of sclera collagen fiber was slightly widened.The photoreceptor layer was more likely to develop a disordered outer segment, which contained deciduous disc membranes.Conclusion Persistent flickering stimulus is attended by development of excessive ocular enlargement,which could affect the retinal structure and function of photoreceptors.