Schistosomiasis is a parasitic disease with more than 200 million people infected worldwide. The formation of granulomas around eggs trapped in the liver is the main cause of disease morbidity. Therefore, the aim of this investigation was to characterize the immunopathological response induced by the recombinant (r) IPSE/alpha-1 egg protein in mice. Herein, we have shown that splenocytes from mice immunized with rIPSE/alpha-1 produced IFN-gamma, TNF-alpha, IL-4, IL-5 and IL-13 characterizing a mixed Th1/Th2 type of immune response. Pathological analysis of the liver revealed that there was no alteration in the number of eggs and granulomas; however, we observed an increase in granuloma area in immunized mice. Furthermore, eosinophil peroxidase assay showed that there was no alteration in the eosinophil infiltration in the liver; however, n-acetyl-beta-glucosaminidase measurement revealed an increase in macrophage activity. Despite the alteration in the profile of liver inflammatory cells in rIPSE immunized mice, the production of chemokines such as CCL2, CCL3, CCL5 and CCL11 was unaltered compared with the control group. In conclusion, IPSE/alpha-1 immunization induces a mixed Th1/Th2 type of immune response and enlargement of hepatic granuloma caused by an increased macrophage activity, but does not alter Th2 cytokines following infection.