In the present work, the role of recombinent Interleukin-12 (rIL-12) as an adjuvant to soluble worm antigen preparation (SWAP) in protection against primary murine S. mansoni infection, using certain immunization protocol, was studied. A highly significant statistical increase in resistance (P<0.001) was observed between the group immunized with SWAP and rIL-12 (group I) and those immunized with SWAP only (group II), when each was compared to the infection control group (group III). Moreover, resistance to challenge infection was higher in group I (73.6%) than in group II (66.1%). In comparison to group III, histopathological examination of liver sections of groups I and II showed marked reduction in granuloma sizes, with more reduction in group I to the extent that some ova were seen without cellular reaction around them. Liver necrosis and fibrosis were detected only in the infection control group. In contrast to group III, sections in the small intestine did not show any granulomatous reaction in groups I and II. rIL-12, when administered with SWAP could inhibit mesangial cells proliferation in the kidney glomeruli of mice in group I. However, minimal mesangial cells proliferation was observed in the kidney sections from mice in group II, when compared to the prominent proliferation seen in group III. rIL-12 has a prominent role when administered as an adjuvant to SWAP, against primary murine S. mansoni infection and for preventing granulomatous reaction, decreasing worm burden and increasing resistance to infection.