Gamma delta (gamma delta) T cells are mainly present in mucosa-associated lymphoid tissues, which play an important role in mucosal immunity. In this study, C57BL/6 mice were infected by Schistosoma japonicum and lymphocytes were isolated from the mesenteric lymph node (MLN) to identify changes in the phenotype and function of gamma delta T cells using flow cytometry. Our results indicated that the absolute number of gamma delta T cells from the MLNs of infected mice was significantly higher compared with normal mice (P < 0.05). In addition, the infected gamma delta T cells expressed a high level of the activated molecule CD69 (P < 0.01) and demonstrated an increasing population of CD4(+) gamma delta T cells (P < 0.05). MLN gamma delta T cells secrete interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-9, and IL-17 in response to propylene glycol monomethyl acetate (PMA) plus ionomycin simulation, and the levels of IL-4, IL-9, and IL-17 increased significantly after S. japonicum infection (P < 0.05). Taken together, these findings indicated that S. japonicum infection could induce gamma delta T cell activation, proliferation, and differentiation in the MLN. Moreover, our results indicated that the expression of NKG2D (CD314) was not increased in gamma delta T cells after infection, suggesting that other mechanisms are involved in activating gamma delta T cells. Furthermore, higher expression of programmed death-1 (CD279) but not IL-10 was detected in the gamma delta T cells isolated from infected mice (P < 0.05), suggesting that the function of gamma delta T cells is inhibited gradually over the course of S. japonicum infection.