PURPOSE. The rhodopsin(-/-) C57Bl/6 (rho(-/-)) mouse is a very important model for understanding retinal degenerative diseases. In this study, spectral domain optical coherence tomography (SD-OCT) was used to monitor the dynamic morphological changes in retina of rho(-/-) mice. METHODS. Rho(-/-) mice and wild type C57Bl/6 (B6) mice at the age of 3, 6, 9, and 12 weeks were investigated using SD-OCT to obtain cross-sectional images of the retina. The outer nuclear layer (ONL) thickness was measured. Histological sections were used to compare to the OCT data. Electroretinograms (ERG) were performed to evaluate the physiological change for establishing the relationship between retinal morphology and its functional changes. RESULTS. There was no apparent morphological or functional change in B6 mice at any time point. The SD-OCT measurement showed that the ONL thickness in rho(-/-) mice was significantly decreased from 40.6 mu m to 6.0 mu m from week 3 to week 12 postnatal. Histological examinations identified a similar trend, although the average thickness of ONL from histological sections at these time points was slightly larger (ranging from 55.4 mu m to 14.9 mu m). The ERG in rho(-/-) mice indicated functional changes that were in concordant with morphological changes; a significant linear positive association was identified between the amplitude of b-wave and the ONL thickness. CONCLUSIONS. Our findings confirmed that the functional changes in retina were concordant with morphological changes measured by SD-OCT in vivo, which indicates that SD-OCT can be used as a reliable noninvasive method to monitor the degenerative progression in retinal disease models. Invest Ophthalmol Vis Sci. 2012;53:3967-3972) DOI:10.1167/iovs.12-9716