Abstract Helminths parasites modulate or escape their host’s immune response by different molecular and cellular strategies. One of these is through the interaction of different molecules from their surface with cellular membrane elements of immune cells, modulating signaling pathways. These parasites trigger, control and modulate the early response of macrophages and dendritic cells (DC). The aim of this study is to elucidate the macrophage signaling pathways that are activated in response to a Helminth Parasitic Antigen Fractions (HPAFs) in vitro. Our data show that HPAFs have a biological effect on macrophages. WB analysis using specific anti-phospho-antibodies, showed that the HPAFs can signalize in a time dependent manner. In addition, immunofluorescence experiments showed that HPAFs promote a significant change in macrophages morphology. Different reports indicate that the chemoattraction and change of morphology of the macrophages is an essential step in the host response to different infections. We evaluated the effect of HPAFs on the transcriptional regulation of downstream target genes. Our PCR studies showed that HPAFs-stimulated macrophages could regulate downstream target genes such as TLR-4, Arg-1, Ym-1 and iNOS, showing that HPAFs regulate important signaling pathways in macrophages. Our results suggest that HPAFs may contain molecules that could interact with membrane molecules, activating signaling pathways that are involved in the regulation of the immune response.