Background: Shen-Qi-Jie-Yu-Fang (SJF) is composed of eight Chinese medicinal herbs. It is widely used in traditional Chinese medicine for treating postpartum depression (PPD). Previous studies have shown that SJF treats PPD through the neuroendocrine mechanism. Aim: To further investigate the effect of SJF on the immune system, including the inflammatory response system and CD4(+)CD25(+) regulatory T (T-reg) cells. Materials and methods: Sprague Dawley rats were used to create an animal model of PPD by inducing hormone-simulated pregnancy followed by hormone withdrawal. After hormone withdrawal, the PPD rats were treated with SJF or fluoxetine for 1, 2, and 4 weeks. Levels of T-reg cells in peripheral blood were measured by flow cytometry analysis. Serum interleukin (IL)-1 beta and IL-6 were evaluated by enzyme-linked immunosorbent assay, and gene and protein expressions of IL-1R(I), IL-6R alpha, and gp130 in the hippocampus were observed by reverse-transcription polymerase chain reaction and Western blot. Results: Serum IL-1 beta in PPD rats increased at 2 weeks and declined from then on, while serum IL-6 increased at 1, 2, and 4 weeks. Both IL-1 beta and IL-6 were downregulated by SJF and fluoxetine. Changes in gene and protein expressions of IL-1R(I) and gp130 in PPD rats were consistent with changes in serum IL-1 beta, and were able to be regulated by SJF and fluoxetine. The levels of T-reg cells were negatively correlated with serum IL-1 beta and IL-6, and were decreased in PPD rats. The levels of T-reg cells were increased by SJF and fluoxetine. Conclusion: Dysfunction of proinflammatory cytokines and T-regs in different stages of PPD was attenuated by SJF and fluoxetine through the modulation of serum concentrations of IL-1 beta and IL-6, expressions of IL-1R(I), and gp130 in the hippocampus, and CD4(+)CD25(+) T-reg cells in peripheral blood.