Previous studies have demonstrated that repeated submission of rats to mild hypobaric hypoxia reduces the persistent behavioral and hormonal depressive symptoms induced by exposure to footshock in the learned helplessness paradigm. The aim of this study was to determine whether hypoxic preconditioning of mice can also induce antidepressant- and anxiolytic-like effects that are detectable with the other commonly used behavioral tests, and to determine whether these effects are accompanied by an increase in neuropeptide Y (NPY) in the hippocampus, which may suggest the involvement of NPY in these mechanisms. The intermittent mild hypobaric hypoxia was generated by 2-h exposure of mice to 0.47 atm for 3 consecutive days. In the tail suspension test a significant decrease in the duration of immobility was observed 24 h, but not 48 h after the last hypobaric session. The elevated plus maze trials performed 48 h after preconditioning showed a significant increase in the frequency of open arm entries, a reduction in the duration of closed arm occupancy and substantially more time spent in the open arms in comparison to the control groups. The open field test demonstrated the absence of increases in general activity or unspecific exploratory behavior in hypoxia-preconditioned mice. The EIA test detected a statistically significant but relatively weak increase in the NPY content in the hippocampus 24 h after preconditioning. Together, our data demonstrate that preconditioning of mice with intermittent mild hypobaric hypoxia induces anxiolytic- and antidepressant-like effects. They are accompanied by up-regulation of NPY which may suggest its mechanistic role.