Background To study the morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia (FDHM) in guinea pigs and explore the possible mechanisms of FDHM formation. Methods Forty 3-week-old guinea pigs were randomized into the blank control (Group I, 20 cases) and model groups (20 cases). In the model group, the right eyes of the guinea pigs were sutured for 8 weeks to induce FDHM (Group II) and the left eyes were considered a self-control group (Group III). The refractive errors were measured with retinoscopy. The anterior chamber depth (AC), lens thickness (L), vitreous chamber depth (V) and axial length (AL) were measured using ultrasonometry A. Retinal and scleral morphology and ultrastructural features were observed with light and electron microscopy. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the retina and sclera were detected with a chemical colorimetric assay. Results After 8 weeks of stitching, the refractive errors of Group II changed from (+ 3.59 +/- 0.33) D to (- 7.96 +/- 0.55) D, and these values were significantly higher than those of Group I (+ 0.89 +/- 0.32) D and Group III (- 0.55 +/- 0.49) D (P < 0.05). The vitreous chamber depth (4.12 +/- 0.13) mm and axial length (8.93 +/- 0.22) mm of Group II were significantly longer than those of Group I [(3.71 +/- 0.23) mm and (7.95 +/- 0.37) mm, respectively] and Group III [(3.93 +/- 0.04) mm and (8.01 +/- 0.15) mm, respectively] (P < 0.05). With the prolongation of form deprivation (FD), the retina and scleral tissues showed thinning, the ganglion cell and inner and outer nuclear layers of the retina became decreased, and the arrangement was disordered. In Group II, the SOD activity was significantly lower than that in Group I and Group III; the MDA content was significantly higher than that in Group I and Group III. The differences were statistically significant (P < 0.05). Conclusions These findings suggested that in the FDHM guinea pigs model, the refractive errors, the vitreous chamber depth, and axial length increased significantly with prolongation of monocular FD time, and morphological structural changes in the retina and sclera were observed. Oxygen free radicals might participate in the formation of FDHM.