Recently, Th17 cell-associated responses have received growing attention; however, the role of IL-22 (a cytokines also produced by Th17 cells) in the pathogenesis of systemic lupus erythematosus (SLE) has not been widely explored. In this study, we analyze the frequencies of IL-22-positive CD4+/CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from patients with SLE and their correlations with disease activity and clinical data. Five-color flow cytometry (FCM) was used to assess IL-22 production of CD4+/CD8+ T cells in PBMCs from 31 patients with SLE and 22 healthy control subjects, following stimulation ex vivo with phorbol 12-myristate 13-acetate and ionomycin for 4 h. Results showed that the percentages of IL-22-positive CD4+ T cells were increased in the PBMCs of patients with SLE compared with healthy control subjects, whereas there were no significant differences in the percentages of IL-22-positive CD8+ T cells. There was a strong positive correlation between the proportion of CD4+ T cells expressing IL-22 and SLEDAI score (r _s = 0.65, P < 0.001). Furthermore, the frequencies of IL-22-positive CD4+ T cells were significantly higher in patients with SLE with nephritis than those without nephritis (Z = −2.72, P < 0.01). In conclusion, increased frequencies of IL-22-positive CD4+ T cells in patients with SLE and positive correlation with SLEDAI score and lupus nephritis suggest that this cytokine may be implicated in the pathogenesis of the disease.