Obesity is a worldwide epidemic being the main cause of cardiovascular and metabolic disturbances (1). Modulation of carotid body (CB) activity, via resection or electrical modulation of carotid sinus nerve (CSN), restores insulin sensitivity and glucose tolerance and decreases weight gain and body fat mass, as well as, normalizes whole-body sympathetic nervous system activity (SNS) in the rat (2-5) and mice. Knowing that CB signals modulate SNS activity, herein we investigated the contribution of β2-adrenergic signalling to the beneficial effects of CSN resection in dysmetabolic states. Experiments were performed in 4 weeks male C57BL/6J and β2-adrenergic receptor knockout (β2-AR-/-) mice (n=3-6) fed with high-fat diet (HF) (5.1Kcal/g) or with a standard diet (2.56Kcal/g) during 12 weeks. After this period, animals were submitted to bilateral CSN resection or to a sham procedure and kept under the respective diets for more 3 weeks. Insulin sensitivity, glucose tolerance, caloric intake and body weight were monitored. One- and two-way Anova with Bonferroni’s multiple comparisons test were used. Data were present as mean ± S.E.M. Experimental protocols were approved by the local and national ethical committee (CIEPAL #2018082016528754). Insulin sensitivity was not altered in β2-AR-/- mice (AUC β2-AR-/-control=10968±1330 mg/dl*min vs. Wild-type (WT)control=11135±584). However, HF diet induced insulin resistance in β2-AR-/- mice (β2-AR-/-HF =22696±1946mg/dl*min) (p<0.05), effects that were similar in the WT animals (WTHF=22336±2069mg/dl*min) (p<0.0001) and were restored 3 weeks after CSN resection. Moreover, glucose tolerance was not modified in β2-AR-/- mice and the HF diet decreased by 25 and 37% (p<0.01) the glucose tolerance in β2-AR-/- and WT mice, respectively, an effect that was improved 2 weeks after CSN resection. Additionally, body weight increase was similar between WT and β2-AR-/- mice both in control and in animals submitted to the HF diet. The CSN resection decreased by 115 (p<0.0001) and 122% (p<0.0001) the weight increase in WT and β2-AR-/- mice, respectively. We conclude that the role of CB in the control of glucose homeostasis and the regulation of weight is not mediated by β2-adrenergic receptors.   *Equally shared last authorship