Differential sensing of dietary fat and fatty acids by the oral cavity is proposed to regulate the susceptibility to obesity. In the current experiments, animals which differ in their susceptibility to obesity were used to investigate the influence of the oral cavity on the preference for the polyunsaturated fatty acid, linoleic acid. In Experiment 1, the preference for differing concentrations of linoleic acid was determined in obesity-prone, Osborne-Mendel (OM) and obesity-resistant S5B/Pl (S5B) rats. The preference threshold for linoleic acid was lower in S5B rats, compared to OM rats. To determine if differences in linoleic acid preference threshold were related to innate strain differences fatty acid receptors on the tongue, the expression of GPR120, GPR40 and CD36 on the circumvallate papillae were assessed in OM and S5B rats. Results indicated that the expression of CD36, GPR40 and GPR120 did not differ between these two strains. Numerous studies have examined the role of CD36 on fat intake, therefore in Experiment 3, RNA interference was used to decrease the expression of CD36 on the tongues of OM and S5B rats and the effect of decreased CD36 expression on linoleic acid preference was determined. CD36 siRNA attenuated linoleic acid preference for the most preferred concentration in both OM and S5B rats. Overall these data indicate that there are innate differences in the preference threshold for linoleic acid in obesity-prone and obesity-resistant rats. Experimentally reducing the expression of CD36 on the circumvallate papillae attenuated the preference for linoleic acid in both strains.