Hydrogen sulfide (H2S) is a naturally occurring gas that is also associated with several industries. The potential for widespread human inhalation exposure to this toxic gas is a public health concern. The nasal epithelium is especially susceptible to H2S-induced pathology. Injury to and regeneration of the nasal respiratory mucosa occurred in animals with ongoing H2S exposure, suggesting that the regenerated respiratory epithelium under-goes an adaptive response and becomes resistant to further injury. To better understand this response, ten-week-old male Sprague-Dawley rats were exposed nose-only to either air or 200 ppm H2S for three hours per day for one day or five consecutive days. Nasal respiratory epithelial cells at the site of injury and regeneration were laser capture microdissected, and gene expression profiles were generated at three, six, and twenty-four hours after the initial three-hour exposure and at twenty-four hours after the fifth exposure using the Affymetrix Rat Genome 230 2.0 microarray. Gene ontology enrichment analysis showed that H2S exposure altered gene expression associated with a variety of biological processes, including cell cycle regulation, protein kinase regulation, and cytoskeletal organization and biogenesis. Surprisingly, our results did not show a significant change in cytochrome oxidase gene expression or bioenergetics.