Renal medulla is a major site for production and action of prostaglandins (PGs). The renal medullary functions as well as structural integrity are in part dependent on PGs under certain physiological or pathophysiological conditions. The two COX isoforms, COX-1 (constitutive form) and COX-2 (inducible form) are both abundantly expressed in renal inner medulla at basal state, raising a question of which COX isoform may mediate the known functions of PGs in the region. As in many other cell types, COX-1 expression in renal medulla is unlikely subject to robust regulation. In contrast, COX-2 expression in renal medulla is markedly stimulated by chronic salt loading, dehydration and endotoxaemia in vivo. At cellular levels, the signalling pathways responsible for the COX-2 stimulation in renal medullary cells seem to involve both the mitogen-activated protein kinases and NF-kappa B. It is likely that in response to various insults that are detrimental to renal medulla, the induction of PG synthesis may become more dependent on COX-2 than COX-1, and this phenomenon may be relevant to the cytoprotective response against the insults.