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To investigate the normal palpebral conjunctival histology in C57BL/6 mice and the structural changes that occur in a dry eye model.Twenty-four male and female C57BL/6 mice, 8 untreated and 16 exposed to experimental ocular surface desiccating stress (DS). Ocular dryness was induced by administration of scopolamine hydrobromide (0.5 mg/0.2 mL) four times a day for 5 days (DS5) or 10 days (DS10). Counts and measurements were obtained using anatomical reference points, and goblet cell density was investigated with a variety of stains.Near the junction between the lid margin and the normal palpebral conjunctiva, the epithelium had an average thickness of 45.6 ± 10.5 μm, 8.8 ± 2.0 cell layers, versus 37.7 ± 5.6 μm, 7.4 ± 1.3 layers in DS10 (P < 0.05). In the goblet cell–populated palpebral region, the normal epithelium was thicker (P < 0.05) than on DS5 and DS10. In the control, 43% of the goblet cells were covered by squamous epithelium compared with 58% (DS5) and 63% (DS10) (P < 0.05). A decreased number of periodic acid–Schiff (PAS)–stained goblet cells and Alcian blue–stained goblet cells were observed in the dry eye. Not all goblet cells were stained with PAS and Alcian blue.The mouse palpebral conjunctival epithelium was structurally similar to the human. After DS, the palpebral conjunctival epithelium decreased in thickness and goblet cell access to the surface seemed to be inhibited by surrounding epithelial cells, potentially slowing down their migration to the surface. Differential staining with PAS and Alcian blue suggests that there may be different subtypes of conjunctival goblet cells.