The  adrenal medullary chromaffin cells are important in generating the acute stress response. This occurs in situations were homeostasis is threatened, or perceived to be so, and can result from various physical and psychological stressors. Studies have suggested that immune challenge can also be considered a form of stress. Previous experiments have shown bovine chromaffin cells are responsive to interleukin-6 (IL-6), with rapid changes in intracellular signals such as Signal Transducer and Activator of Transcription 3 (STAT3) and extracellular signal-regulated kinases 1/2 (ERK1/2). Additionally, IL-6 is known to induce chronic increases in the expression of specific neuropeptides including parathyroid-related peptide, gastrin releasing peptide and vasoactive intestinal polypeptide. The following experiments were conducted to investigate whether similar responses can be observed in vivo using a mouse model. The first aim was to determine whether murine chromaffin cells express IL-6 receptor (IL-6R). mRNA was extracted from the adrenal medulla of male mice and processed for RT-PCR. Dual-label fluorescent immunohistochemistry was performed, using antibodies to IL-6R and tyrosine hydroxylase (a marker of chromaffin cells). IL-6R mRNA expression was detected in the adrenal medulla, and immunohistochemistry confirmed its translation into protein within the chromaffin cells. To investigate receptor activation in the presence of IL-6, male mice were treated intraperitoneally with or without 1μg IL-6 30 min prior to euthanasia. The adrenal glands were sectioned and processed for immunohistochemistry using antibodies against phosphorylated STAT3 and phosphorylated ERK1/2. An increase of both pSTAT3 and pERK1/2 was observed in IL-6 treated mice compared to saline treated controls. These results suggest the mouse adrenal medulla is responsive to IL-6 in vivo. Future experiments will investigate the downstream consequences of these responses, and consider the role of immune-adrenal interactions in health and pathology.