Background: The relationship between depression and adaptive immunity has gradually attracted increasing attentions. However, no consistent conclusions have been drawn about alterations in adaptive immunity in depression. Methods: Eight-week-old weight-matched male C57BL/6 mice were randomly divided into a chronic unpredictable mild stress (CUMS) model group and a control group, with twelve mice in each group. After 8-week CUMS modeling duration and depressive behavioral tests, T cell responses were evaluated at the cell, cytokine, and cell-specific transcription factor levels. Lymphocytes in the spleen were detected by flow cytometry; serum cytokines were assessed by enzyme-linked immunosorbent assays; expression levels of cytokines and cell-specific transcription factors in the hippocampus were determined by quantitative PCR. Results: CUMS exposure induced depression-like behaviors with decreased sucrose preference and longer immobility time in the tail suspension test and forced swim test. The CUMS group had a lower proportion of CD4(+) T cells than the control group. A decreased number of T helper 17 (Th17) cells in the spleen and down regulated serum interleukin (IL)-17 and hippocampal retinoid-related orphan receptor-gamma t levels were detected in the CUMS group. Depressed mice in the CUMS group showed increases in serum IL-1 beta and IL-6 and hippocampal IL-6 and IL-4 levels. Limitation: The study was based on a mouse model. Further studies are needed to determine whether the results are applicable to patients with depression. Conclusion: CUMS exposure can induce depression-like behaviors and decrease Th17 cell counts.