Summary We have previously shown that oxidative stress is involved in the pathogenesis of a mercuric chloride (HgCl2)‐induced, T helper type 2 (Th2)‐driven autoimmune syndrome in Brown Norway (BN) rats. In the context of the syndrome, the oxidative stress‐induced mast cell response seems to determine the development of the early phase of vasculitis, while oxidative stress‐mediated interleukin (IL)‐4 production may contribute to the subsequent Th2‐driven autoimmune response. However, the molecular basis of IL‐4 gene transcription induced by HgCl2 in mast cells remains unknown. In the present study, we dissect the critical regulatory mechanisms in the IL‐4 gene promoter in the rat mast cell line RBL‐2H3. Immunoprecipitation provided evidence that treatment with HgCl2 increased phosphorylation of signal transducer and activator of transcription 6 (STAT6). Transient transfection reporter analyses with a series of 5′ end deletions of the IL‐4 promoter produced evidence that STAT6 and TATA box binding sites are important in HgCl2‐induced IL‐4 gene expression. Subsequent elimination of one or both sites by site‐directed mutagenesis significantly inhibited IL‐4 promoter activity. Our results provide evidence that STAT6 and TATA box regulatory elements play an important role in HgCl2‐induced IL‐4 transcription in rat mast cells.