Objective To observe the influence of dexamethasone on the gene expression profiling of PBMCs from patients with internal heat due to Yin deficiency-type SLE. Methods The PBMCs from 3 patients with internal heat due to Yin deficiency-type SLE were incubated with dexamethasone of 10-6 g/L for 48 hours followed by the detection of gene expression profiling of PBMCs by a GeneChip. Results The incubation with dexamethasone upregulated the expressions of 85 genes and downregulated those of 126 genes in PBMCs from the SLE patients. Conclusions Dexamethasone can regulate the expressions of numerous clusters of genes in PBMCs from patients with internal heat due to Yin deficiency-type SLE, and functional proteins encoded by these genes are located at various organelles and regions of cells. Not all the results of gene regulation by dexamethasone favor the relief of SLE. To study the regulation of genes may be beneficial to the elucidation of mechanisms underlying the therapeutic effect of dexamethasone on SLE.