Humoral and cellular immune responses to Fasciola gigantica experimental infection in buffaloes were studied. The results showed that 33.4+/-9.1% of the infection dose was recovered as adult flukes from infected animals at necropsy. Significant differences of weight gain between infected and non-infected buffaloes was observed at 4 MPI (months post-infection). Anti F. gigantica excretory-secretory products (FgESP)-IgG levels increased significantly from 3 WPI (weeks post-infection) and displayed a peak at 13 WPI. Western blot indicated that in FgESP six major bands of 11.5, 19.0, 23.4, 29.8, 47.5 and 53.2kDa were recognized by F. gigantica-infected buffaloes sera after 0 WPI. Eosinophil numbers increased significantly from 3 WPI in F. gigantica-infected buffaloes and displayed a peak at 8 WPI. Peripheral blood mononuclear cells (PBMC) proliferation induced by FgESP increased from 2 WPI with a peak at 5 WPI. IFNgamma secretion by FgESP-stimulated PBMC appeared early from 1 WPI with three peaks at 2, 5 and 8 WPI, respectively. IL-10 production was observed from 2 WPI with two peaks at 4 and 9 WPI, respectively. Our results suggested that buffaloes were highly susceptible to F. gigantica infection, and this susceptibility could be associated with the late and weak cellular immune response in the early phase of infection and the Th0-like response throughout the infection.