Host immune response against Schistosoma mansoni is a major contributor in the process of resistance or susceptibility to re-infection, as well as the therapeutic response towards different antischistosomal drugs. This study evaluated the role of IgG &IgG4 as immune-logical marker of cure and their effect on anti-schistosomal mefloquine efficacy. Sixty Swiss albino mice were infected with Schistosoma cercaria and divided into four groups; non-infected, infected not treated, infected treated with praziquantel and infected treated with mefloquine. The effect of drugs was assessed parasitologically using Kato-Katz technique and immunologically by measuring the serum level of anti-Schistosoma IgG & IgG4 subclass. The results showed 83.5% significant egg count reduction in MFQ-treated infected group. Also, serum anti-soluble egg antigen (SEA) total IgG & IgG4 subclass levels in MFQ treated group were significantly different from infected control group & PZQ-treated infected group.