Background: This study explored the details of the immune response after autologous hematopoietic stem cell transplantation (AHSCT) treatment in type 1 diabetes mellitus. Methods: Peripheral blood mononuclear cells (PBMCs) from 18 patients with type 1 diabetes mellitus were taken at baseline and 12 months after AHSCT or insulin-only therapy. The lymphocyte proliferation, mRNA expression and secretion of pro-inflammatory and anti-inflammatory cytokines belonging to T-helper type 1 (Th1), T-helper type 17 (Th17) and regulatory T (Treg) cells in PBMC culture supernatants were assessed. Results: Compared with patients receiving insulin-only treatment, the patients receiving AHSCT treatment showed better residual C-peptide secretion, lower anti-GAD titers and less exogenous insulin dosages after 12 months of follow-up. AHSCT treatment was associated with significantly reduced Th1 and Th17 cell proportions as well as decreased IFN-gamma, IL-2, IL-12p40 and IL-17A levels in the PBMC culture supernatants (all P < 0.05). Although there was no significant Treg cell expansion after AHSCT treatment, we observed increased IL-10, TGF-beta and Foxp3 mRNA expression and increased TGF-beta levels. However, we found no significant changes in the T-cell subpopulations after insulin treatment, except for higher IL-12p40 mRNA expression and a lower proportion of Treg cells. Conclusions: AHSCT treatment was associated with decreased expansion and function of Th1 and Th17 cells, which may explain the better therapeutic effect of AHSCT compared with the traditional intensive insulin therapy.