Metallothioneins (MTs) are involved in the cellular metabolism of zinc and in cytoprotection against stress factors. Hippocampus plays a specific role in the body's response to stressors. The present study was conducted to evaluate the effects of zinc on the expression of metallothionein isoforms in the hippocampus of stress rats. The animal model of psychologic stress was developed by restraint for 4 weeks. Wistar rats were randomly assigned to 6 groups: control group, zinc-deficient group, zinc-supplemented group, and the corresponding 3 stress groups. Three separate diets of different zinc contents (1.73 ppm, 17.7 ppm, and 41.4 ppm, respectively) were used in this study. Compared with the control group, the stress groups had higher inductions of MTs and MT-1 and MT-3 mRNA in hippocampus. On the one hand, the expressions of MTs and their mRNAs in hippocampus were downregulated in the zinc-deficient group; however, their expressions were evidently enhanced in the stress zinc-deficient group. MT induction in the zinc-supplemented group was increased. Furthermore, the stress zinc-supplemented group had a more significant yield of MTs and their mRNAs. In addition, the levels of plasma cortisol, interleukin-6 (IL-6), IL-1, and nitric oxide (NO) were increased clearly in the zinc-deficient group and the stress groups. The results suggest that zinc deficiency may decrease and zinc supplementation may increase the expressions of MTs and their mRNAs in hippocampus; moreover, stress can increase their expressions dramatically. The impairment of stress on the body may be involved with the nutrition status of zinc, and zinc deficiency can lower the body's adaptability to stress.