Chronic exposure to drugs of abuse, including alcohol, produces long-term neuroadaptations in the central nervous system, which are believed to contribute to both the maintenance of ongoing drug use and persistent vulnerability to relapse. It is hypothesized that part of this neuroplasticity involves sensitization to stimulus cues that are repeatedly and reliably associated with drug administration. Due to its oral route of administration, the chemosensory cues accompanying alcohol consumption are among the most intimate and consistent stimuli immediately predictive of the drug's subsequent postabsorptive effects. In alcoholics and high risk drinkers, alcohol chemosensory stimuli elicit urges to drink as well as activation of mesocorticolimbic structures implicated in drug-seeking and motivation, and in animal models of relapse, re-exposure to ethanol taste cues following extinction of ethanol self-administration induces strong reinstatement of ethanol-seeking. Recent evidence has implicated the insular cortex as a significant brain region of interest involved in the processing of drug-associated stimuli. Functional imaging studies in humans have revealed insular activation during the experience of drug-related craving and exposure to drug-associated cues, and inactivation of the insula in rodents has been shown to prevent cue-induced reinstatement of nicotine- and cocaine-seeking and to disrupt conditioned preference for environments previously paired with nicotine or amphetamine. Anatomically, the insula is centrally situated to integrate information regarding ethanol chemosensory signals with the drug's postingestive effects, receiving visceral interoceptive and gustatory input from the thalamus and possessing reciprocal connections to limbic structures important in reward and motivation. Prior evidence has indicated that neuroplasticity within the insular cortex (IC) accompanying chemosensory learning may be reflected by changes in both the magnitude and/or pattern of neuronal response to a chemosensory stimulus. To date, no studies have addressed the potential role of the IC in processing learned associations between alcohol chemosensory cues and the drug's postingestive reinforcing effects following chronic exposure. The objective of this study was to investigate changes in the central processing of ethanol orosensory signals within the IC following chronic experience with the drug. Outbred Wistar rats (n = 12/group) were initially exposed for 5 weeks to either a 20% ethanol or 0.5% saccharin intermittent-access drinking paradigm or were given access only to water (naive). Following the chronic drinking phase, naive and experienced rats from each stimulus condition were allowed to consume a fixed volume of their respective exposure stimulus (20% ethanol or 0.5% saccharin) and neuronal Fos response within the gustatory insula was measured 90-min post-exposure. Oral administration of 20% ethanol produced robust activation of the gustatory insula in naive rats, which was significantly reduced in alcohol-experienced animals. A trend for a similar reduction in tastant-elicited Fos expression was observed in saccharin-exposed subjects. These data suggest that gustatory regions of the insula may process information relevant to the novelty/familiarity of ethanol taste similar to other appetitive tastants.