Two experiments were conducted to study the effects of an in ovo interleukin (IL)-4 plasmid injection in a coccidia infection model. In experiment I, chicks were hatched from eggs that had been injected in ovo with an empty vector or with 10 or 15 μg of IL-4 plasmid, and then challenged posthatch with coccidia. In experiment II, chicks were hatched from eggs that had been vaccinated with coccidia and injected in ovo with an empty vector or with 10 or 15 μg of IL-4 plasmid, and then challenged posthatch with coccidia. In experiment II, the BW gain of birds hatched from eggs vaccinated with live oocysts plus 15 μg of IL-4 plasmid was 25% higher than the BW gain of birds hatched from eggs vaccinated with live oocysts plus empty plasmid. In both experiments I and II, a 15-μg IL-4-plasmid injection decreased fecal oocyst shedding, decreased the number of CD8(+) cells in the cecal tonsils, and decreased cecal tonsil lymphocyte cell proliferation postcoccidia challenge. In experiment I, splenic macrophages of chicks hatched from eggs injected with 15 μg of IL-4 plasmid had higher nitric oxide production than those of chicks hatched from eggs injected with the empty plasmid. In experiment II, a 15-μg IL-4-plasmid injection increased serum anticoccidia IgG postcoccidia challenge. It could be concluded that 15 μg of IL-4 plasmid improved anticoccidia immune responses synergistically with in ovo coccidia vaccination in chickens.