The effects of zinc chloride (ZnCl2), disodium zinc ethylenediamine tetraacetate (Zn-EDTA), and zinc gluconate (Zn-GLU) on the antioxidant enzyme activities and levels of interleukins (ILs) in psoriasis-induced mice were studied. One hundred twenty female mice were randomly divided into six groups with 20 mice in each group: the control, positive control (PC), methotrexate (MTX), ZnCl2, Zn-EDTA, and Zn-GLU groups. All animals except the control group were given diethylstilbestrol for three consecutive days. After successfully inducing psoriasis, the control and PC groups were given normal saline (i.g.) daily while the remaining groups were given MTX, ZnCl2, Zn-EDTA, and Zn-GLU, respectively. The results revealed that the zinc supplementation could significantly (p < 0.05) inhibit mitosis in the mouse vaginal epithelium as methotrexate did and the inhibiting efficacy had nothing to do with the zinc forms. After ZnCl2, Zn-EDTA, and Zn-GLU supplementation, the levels of liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities increased and the concentration of malondialdehyde (MDA) decreased significantly (p < 0.05) compared to the PC group. The levels of SOD, CAT activity, and MDA level between each zinc supplementation group and MTX group were insignificant (p > 0.05). The zinc treatments also caused a significant (p < 0.05) decrease in the raised IL-2 level of animal serum. The results obtained in the present work indicate the potential for zinc as a complementary pharmaceutical intervention for the treatment of topical psoriasis.