During blood feeding Aedes aegypti mosquito introduce salivary proteins into the host skin to facilitate a successful blood meal acquisition. These salivary proteins also modulate the transmission of pathogens like Zika (ZIKV). Sialokinin I (SK1) is a member of the tachykinin family, present in saliva of Ae. aegypti mosquitoes and functions as a potent vasodilator. Human tachykinin is involved in mast cell activation and inflammation. Interestingly, this protein is very similar to the vertebrate tachykinin, Substance P. In this work, we explored the mast cell responses to SK1 and its effect on ZIKV infection. We found that incubation of mast cells with recombinant SK1 significantly upregulates CXCR4 and TNFα. When SK1-treated mast cells were co-cultured with neurons, we found that TOLLIP, CLL2 and MYD88 were significantly upregulated. We conclude that the salivary neuropeptide SK1 may have an important role in inflammatory responses in skin adjacent tissues.