Glucocorticoids (GC) have been widely used to treat patients with systemic lupus erythematosus (SLE). However, GC-insensitivity remains a major barrier in achieving remission. Therefore, understanding its mechanism is crucial to enhance the efficacy of GC treatment. Our study aimed to explore the association of the nuclear receptor subfamily 3 group C member 1 (NR3C1) gene, which encodes GC receptors GRα and GRβ, the histone deacetylase2 (HDAC2), the histone acetyltransferase-1 (HAT1), and the interleukin- 23 receptor (IL-23R), with the response to treatment in SLE patients. Methods:  Quantitative real-time PCR (qPCR) was used to determine the expression levels of NR3C1 isoforms, HDAC2, HAT1, and IL23R in peripheral blood mononuclear cells (PBMC) from 30 SLE patients and 6 healthy controls (HC). Immunohistochemical (IHC) staining was used to analyze the protein expression level of GRα in 19 SLE patients’ 8 controls renal biopsies.  Results: GRα mRNA expression level was associated with SLE disease (p=0.018) and correlated with the SLEDAI score (p=0,038).  HDAC2 was up-regulated in patients during remission phase compared to active phase (p=0.015). The IL23R mRNA expression was associated with anemia (p=0.037) and lymphopenia (p=0.028). It was up-regulated in treated patients with the combination of hydroxychloroquine, cyclophosphamide, and methylprednisolone (p=0,028) compared to other treatments. Tubular GRα expression showed a positive correlation with the chronicity index (rs=0.607, p=0.016).  Conclusion: The GRα may be involved in the pathogenesis of SLE. It appears that HDAC2 contributes to the remission phase in SLE. IL23R expression could be affected by treatments in SLE patients.