The vasoactive intestinal peptide (VIP) expression is lower in cardiac chagasic patients and is related to worse cardiac function. The reduction of VIP in patients with Chagas disease may be a result of its enhanced degradation. To test this hypothesis, the tryptase and chymase expression was evaluated. We also related VIP levels with interleukin-17 (IL-17) expression since VIP may modulate IL-17 production. Plasma levels of chymase were higher in chagasic patients. Conversely, VIP/chymase and VIP/tryptase ratios were lower in chagasic patients when compared to non-infected individuals. Besides, the VIP/chymase ratio was lower in chagasic cardiac patients in comparison with the indeterminate group. A positive correlation between tryptase and chymase levels was observed in chagasic cardiac patients. In relation to IL-17, we observed a higher expression of this cytokine in the cardiac form of the disease than in the indeterminate form. IL-17/VIP ratio was higher in the cardiac form in comparison with non-infected or indeterminate form. These results suggest that the low levels of VIP observed in chagasic patients could be due to an increased production of chymase and/or to the additive effect of the interaction between chymase and tryptase in the cardiac form. Moreover, the decreased VIP expression may contribute to the increase of IL-17 in chagasic cardiac patients.