Purpose: Spectral domain optical coherence tomography (SD-OCT) allows cross-sectional visualization of retinal structures in vivo. Here, we report the efficacy of a commercially available SD-OCT device to study mouse models of retinal degeneration. Methods: C57BL/6 and BALB/c wild type mice and three different mouse models of hereditary retinal degeneration (Rho(-/-), rd1, RPE65(-/-)) were investigated using confocal scanning laser ophthalmoscopy (cSLO) for en face visualization and SD-OCT for cross-sectional imaging of retinal structures. Histology was performed to correlate structural findings in SD-OCT with light microscopic data. Results: In C57BL/6 and BALB/c mice, cSLO and SD-OCT imaging provided structural details of frequently used control animals (central retinal thickness, CRTC57BL/6 = 237+/-2microm and CRTBALB/c = 211+/-10microm). RPE65-/- mice at 11 months of age showed a significant reduction of retinal thickness (CRTRPE65 = 193+/-2microm) with thinning of the outer nuclear layer. Rho-/- mice at P28 demonstrated degenerative changes mainly in the outer retinal layers (CRTRho = 193+/-2microm). Examining rd1 animals before and after the onset of retinal degeneration allowed to monitor disease progression (CRTrd1 P11 = 246+/-4microm, CRTrd1 P28 = 143+/-4microm). Correlation of CRT assessed by histology and SD-OCT was high (r(2) = 0.897). Conclusion: We demonstrated cross sectional visualization of retinal structures in wild type mice and mouse models for retinal degeneration in vivo using a commercially available SD-OCT device. This method will help to reduce numbers of animals needed per study by allowing longitudinal study designs and facilitate characterization of disease dynamics and evaluation of putative therapeutic effects following experimental interventions.