This study examined the reaction of the local vasculature of the oral mucosa in 16 Sprague Dawley rats receiving systemic nicotine delivered (1.5 mg/kg/day) via subcutaneous minipumps for 24 h or 2wk. Control animals received saline. After treatment animals were killed and biopsies taken from palate, maxillary gingiva and buccal mucosa, frozen and cryostat sections incubated to demonstrate alkaline phosphatase, which is a capillary marker. The total length of the capillary fragments in the nicotine treated groups was significantly less than of the control group. There was also a decrease in capillary height in both of the nicotine groups when compared to the control animals. This study indicates that morphologic alterations occur in the microvasculature of the oral mucosa following systemic nicotine administration. This may have implications for the role of chronic tobacco use in the etiology of oral mucosal disease, including periodontal disease.