Background. Estimates suggest that approximatively 25% of the world population will be overweight in 2025. Better understanding of the pathophysiology of obesity will help to develop future therapeutics. Serotonin subtype 6 receptors (5-HT 6 ) have been shown to be critically involved in appetite reduction and weight loss. However, it is not known if the pathological cascade triggered by obesity modifies the density of 5-HT 6 receptors in the brain. Methods. Influence of diet-induced obesity (DIO) in Wistar rats was explored using MRI (whole-body fat) and PET ([ 18 F]2FNQ1P as a specific 5-HT 6 radiotracer). The primary goal was to monitor the 5-HT 6 receptor density before and after a 10-week diet (DIO group). The secondary goal was to compare 5-HT 6 receptor densities between DIO group, Wistar control diet group, Zucker rats (with genetic obesity) and Zucker lean strain rats. Results. Wistar rats fed with high-fat diet showed higher body fat gain than Wistar control diet rats on MRI. [ 18 F]2FNQ1P PET analysis highlighted significant clusters of voxels (located in hippocampus, striatum, cingulate, temporal cortex and brainstem) with increased binding after high-fat diet (p< 0.05, FWE corrected). Conclusion. This study sheds a new light on the influence of high-fat diet on 5-HT 6 receptors. This study also positions [ 18 F]2FNQ1P PET as an innovative tool to explore neuronal consequences of obesity or eating disorder pathophysiology.