Obesity is a worldwide epidemic and a risk factor for cardiovascular diseases, and it is associated with a sympathetic overactivation to different organs that could be involved in obesity-associated hypertension. Moreover, it has been shown that the hypothalamic inflammation induced by high fat diet can alter the neurotransmission of autonomic centers leading to increases in the blood pressure. Here we screened the hypothalamus of diet-induced obesity in mice for neuropeptides and inflammatory factors that could be involved in the changes in mean arterial pressure (MAP) associated with obesity. Male mice C57BL6 submitted to high fat (HF; 60%kcal lipids) or control (C) diet for 8 weeks were evaluated for body weight gain, glucose tolerance, adiposity and plasma levels of leptin, insulin, triglycerides and free fatty acids. Femoral catheterization was performed under anesthesia with isoflurane (5% in O2-air inspired) and MAP was recorded in conscious freely moving mice. Hypothalamic mRNA of inflammation mediators and neuropeptides were quantified by qPCR. Values are expressed as mean±S.E.M., compared by ANOVA or t-Test; p<0.05. HF mice developed obesity as evidenced by the increased body weight gain (31%) and adiposity (epididymal, retroperitoneal and inguinal fat depots) in comparison to C group. Furthermore, HF diet increased fasting plasma levels of glucose (C: 177±8 vs HF: 200±6 mg/dL); leptin (C: 8±3 vs HF: 17±5 ug/ml), insulin (C: 43±7 vs HF: 672±127 pmol/L), triglycerides (C: 1.0±0.4 vs HF: 2.2±0.6 mmol/L), free fatty acids (C: 0.2±0.1 vs HF: 0.7±0.2 nmol/L), and induced severe glucose intolerance (C: 24106 vs HF: 35170 u.a., p<0,0001). The HF-diet led to two different hemodynamic phenotypes: obese hypertensive (OH: 123±2 mmHg, n=2) and obese resistant hypertension (OR: 102±5 mmHg, n=3) when compared with group C (107±1 mmHg, n=3). The MAP showed strong correlation with the glucose intolerance (r2 = 1.0, n=3). In addition, the HF-diet elicited an increase of the hypothalamic mRNA levels of cocaine- and amphetamine-regulated transcript (CART, +69%, n=5), decreased agouti gene-related peptide (AgRP, -52%, n=5) and interleukin-6 (IL-6, -40%, n=5) when compared to the C group. Our data have shown that high fat diet affected MAP and others obesity-related metabolic changes, such as glucose intolerance, hyperinsulinemia, dyslipidemia, hyperleptinemia, insulin resistance and altered mRNA levels of neuropeptides involved in the regulation of energy balance (CART and AgRP) and cytokines (IL-6) at the hypothalamus level. In fact, there is a great correlation between increasing in MAP and glucose tolerance, that could be also has a causality relationship with changes in neuropeptides and inflammatory factors in the autonomic nucleus of the hypothalamus that control blood pressure.