Histamine is an important neuromodulator involved in the regulation of homeostatic processes, including energy balance. In the brain, histamine generally evokes an anorexigenic response, suppressing food intake via the histamine 1 receptor (H1R) expressed in the hypothalamus. The central histaminergic system has also been implicated in mediating some of the anorectic effects of leptin. However, the exact locations and mechanisms by which histamine and leptin signaling interact remain to be identified. Therefore, we aimed to determine if leptin influences the electrical excitability of posterior hypothalamic neurons expressing histidine decarboxylase (HDC), the sole enzyme required for histamine synthesis. Whole-cell patch-clamp electrophysiology and c-Fos experiments were performed in mice expressing tdTomato fluorescence in all Hdc expressing cells (Hdc-Cre). Gene expression experiments were performed in C57Bl6J mice. Whole-cell voltage-clamp experiments revealed that leptin (100nM) does not alter the amplitude or frequency of excitatory (EPSCs) or inhibitory (IPSCs) post synaptic inputs arriving at histaminergic neurons. Consistent with these findings, intracerebroventricular (ICV) administration of leptin (2µg) did not alter markers of neuron activity (c-Fos) in Hdc-expressing neurons. Furthermore, Hdc gene expression remained unchanged in the hypothalamus following ICV administration of leptin. Together, these data suggest that leptin does not regulate the activity of histaminergic neurons and that the interaction between histamine and leptin signaling is downstream of the histaminergic neurons.