When mosquitoes probe to feed blood, they inoculate a mixture of salivary molecules into vertebrate hosts' skin causing acute inflammatory reactions where mast cell-derived mediators are involved. Mosquito saliva contains many proteins with largely unknown biological functions. Here, two Aedes albopictus salivary proteins - adenosine deaminase (alADA) and al34k2 - were investigated for their immunological impact on mast cells and two mast cell-specific proteases, the tryptase and the chymase. Mouse bone marrow-derived mast cells were challenged with increased concentrations of recombinant alADA or al34k2 for 1, 3, and 6 h, and to measure mast cell activation, the activity levels of β-hexosaminidase and tryptase and secretion of IL-6 were evaluated. In addition, a direct interaction between alADA or al34k2 with tryptase or chymase was investigated. Results show that bone marrow-derived mast cells challenged with 10 μg/ml of alADA secreted significant levels of β-hexosaminidase, tryptase, and IL-6. Furthermore, both al34k2 and alADA are cut by human tryptase and chymase. Interestingly, al34k2 dose-dependently enhance enzymatic activity of both tryptase and chymase. In contrast, while alADA enhances the enzymatic activity of tryptase, chymase activity was inhibited. Our finding suggests that alADA and al34k2 via interaction with mast cell-specific proteases tryptase and chymase modulate mast cell-driven immune response in the local skin microenvironment. alADA- and al34k2-mediated modulation of tryptase and chymase may also recruit more inflammatory cells and induce vascular leakage, which may contribute to the inflammatory responses at the mosquito bite site.