In the present study, an attempt was made to compare three stress models and their effects on the hypothalamic-pituitary-adrenal (HPA) axis, the thymus, the thyroid hormones and the glucose levels. The three different stress models were the chronic mild stress (CMS), the 14-day and the 1-day cold swim stress model. The CMS procedure caused a decrease in thymus weight and rendered no changes on glucose, the adrenocorticotropin hormone (ACTH) or the adrenals. Administration of imipramine (IMI) after the third week of CMS did not reverse the decrease in thymus weight. The 14-day cold swim stress doubled ACTH levels and the adrenal weight and reduced thymus weight, while total thyroxine (tT4), total triiodothyronine (tT3) and glucose levels were unaffected. IMI treatment restored the weights of the adrenal and thymus glands. One-day cold swim stress did not induce any statistically significant effect on the tested physiological parameters. The above findings indicate a distinct effect of the 14-day cold swim stress on HPA axis. Relative to CMS or the 14-day cold swim stress, no effect was induced by the 1-day cold swim stress. The IMI restoring effect, especially in the case of the 14-day cold swim stress, also suggests an association of antidepressant effect with the duration of drug treatment.