Breakdown of immune homeostasis contributes to the pathogenesis of systemic lupus erythematosus (SLE). Tumor necrosis factor alpha induced protein-8 like-2 (TIPE2) is a very recently identified immune homeostasis maintaining gene. We wondered whether TIPE2 is associated with SLE. We examined the mRNA expression levels of TIPE2 and myxoma resistance protein (MX) 1 (one of type I interferon inducible genes) in peripheral blood mononuclear cells (PBMC) from 39 SLE patients and 35 healthy controls by real-time reverse transcription-polymerase chain reaction analysis (RT-PCR). The TIPE2 mRNA expression was significantly down-regulated in SLE patients compared with healthy controls (P=0.0004), while the MX1 mRNA expression was increased in SLE patients compared with healthy controls (P=0.0031). Furthermore, the TIPE2 mRNA expression levels negatively correlate with the SLE disease activity index (SLEDAI) (r=-0.5016, P=0.0011) and the MX1 mRNA expression levels (r=-0.8083, P<0.0001) in all the SLE patients. These results indicate that decreased expression of TIPE2 gene is closely associated with SLE and suggest an important role for TIPE2 gene in the pathogenesis of SLE.