Both high-fat and high-carbohydrate diets have been considered in association with the impairment of baroreflex sensitivity. However, the mechanisms are unclear. In the present study, the effects of a complex high-fat and high-carbohydrate diet (HFCD) on baroreflex circuitry were investigated. A HFCD emulsion was formulated and orally administered to rats for 30 d. Rats were then anaesthetised and baroreflex sensitivity was measured following intravenous injection of phenylephrine (PE) and sodium nitroprusside (SNP) at various doses. Morphological changes of the brainstem were detected by transmission electron microscopy. Baroreflex sensitivity-associated gene and protein expression was determined by quantitative RT-PCR and Western blot analysis. We found that: (1) the HFCD significantly attenuated heart rate responses to arterial blood pressure (ABP) increases induced by PE, but had no effect on heart rate responses to ABP decreases induced by SNP; (2) the HFCD induced medullary sheath thickening, myelinated nerve atrophy and hyaloplasm dissolving; (3) protein levels of substance P, calcitonin gene-related peptide, GlutR2 and γ-aminobutyric acid A receptors were all markedly decreased in the brainstems of rats administered with the HFCD. These findings conclude that a HFCD could impair the baroreflex sensitivity of rats. Remodelled morphology and decreased neurotransmitters and receptors in the domains of the nucleus tractus solitarii and nucleus ambiguus are participating in this process.