Recent findings indicate that the insular cortex is critically involved in addictive behavior to multiple drugs of abuse. Damage sustained to the insula in addicted smokers results in a disruption of nicotine addiction and pharmacological inactivation of the insula in rodents disrupts conditioned preference for amphetamine-paired environments, decreases nicotine self-administration, and prevents cue-induced reinstatement of nicotine seeking. Human imaging studies have demonstrated activation in the insula in response to drug-associated cues and during the experience of drug-related craving, including craving elicited in heavy drinkers by exposure to the taste of alcohol. To date, no studies have directly manipulated the insular cortex to examine its role in the initial unconditioned processing of alcohol taste information or responses to conditioned alcohol taste cues following experience with the drug. The present study utilized a brief access assay to measure chemosensory responses to alcohol in alcohol-naive and alcohol-experienced rats under conditions of pharmacological "silencing" of caudal granular/dysgranular insular cortex (CGIC). Prior to stereotactic surgery to implant intracranial cannulae, Wistar rats (n=15/group) were exposed for five weeks to either an intermittent-access 20% ethanol-drinking paradigm or were given access only to water. Rats from each exposure condition were subsequently tested over five consecutive days for short-term lick responses to six concentrations of ethanol (3-40%) and a water control after receiving bilateral infusions of either saline or 1 g/l muscimol into CGIC. Psychophysical concentration-response functions to ethanol (mean lick count, trials sampled, and response latency) were generated for each group of animals. To control for specificity of insular inactivation effects on chemosensory responses to ethanol, short-term food intake was measured under each infusion treatment condition one week following ethanol testing procedures. Results indicated significant levels of ethanol intake and preference during the chronic exposure phase, which led to heightened chemosensory cue reactivity to ethanol, reflected by an elevation in mean lick responses/trial, trial sampling frequency, total licks, and a faster latency to initiate sampling for ethanol. Inactivation of the insula eliminated the concentration-dependent preference curve in mean licks/trial for ethanol in chronically exposed animals. Additionally, there were trends for a reduction in total lick responses to ethanol, number of ethanol trials sampled, and an attenuation of exposure effects on response latency for ethanol as a result of insula silencing in alcohol-experienced animals. Insula inactivation did not modify orosensory responses to ethanol in alcohol-naive animals. Food intake measurements revealed that inactivation of the insula also resulted in a moderate (~29%) but significant reduction in food intake regardless of exposure condition. These data support involvement of the interoceptive insular cortex in mediating responsiveness to conditioned alcohol chemosensory cues following chronic association of ethanol's taste and post-absorptive effects. The present findings also indicate that the effects of insula inactivation may extend to other motivated ingestive behaviors.