This study aimed to observe the therapeutic effect of pentapeptide PLNPK on systemic lupus erythematosus (SLE) in mice, and to study the inhibitory effect of PLNPK on activation of T cells in vivo. Murine SLE-like chronic graft-versus-host disease (cGVHD) was induced. After treatment with PLNPK (100, 200, 400 mu g/kg per day) for 70 days, serum blood urea nitrogen, creatine, total cholesterol, triglyeride and albumin were tested, and serum levels of anti-dsDNA and anti-histone antibodies were detected by ELISA. The pathological damage and IgG deposition in the kidney were identified. Concanavalin A (ConA)-induced T lymphocyte proliferation in SLE mice was also tested. PLNPK can reduce serum blood urea nitrogen, creatine, total cholesterol, triglyeride, and elevate serum albumin, and reduce levels of anti-dsDNA and anti-histone antibodies in the murine SLE model. Pathological damage and IgG deposition in the kidney were reduced in the PLNPK-treated group. PLNPK inhibited T lymphocyte infiltration in kidney tissues and ConA-induced T lymphocyte proliferation in SLE mice. Our results demonstrate that PLNPK can suppress T cell function and reduce the production of autoantibodies, and may be a feasible and effective therapy in the SLE model.