C-type natriuretic Peptide (CNP), the third natriuretic peptide (NP) identified, is mainly expressed in the nervous system and endothelial cells. In addition, CNP is believed to be produced locally in tubular cells and glomeruli of normal human kidneys. CNP exerts mainly vasodilatory and antimitogenetic effects rather than regulation of body fluid homeostasis via autocrine or paracrine pathway. Many factors, such as shear, pro-inflammatory cytokines and lipopolysaccharide, can regulate the production and excretion of CNP both in vivo and in vitro. However, little information about the renal action of CNP was obtained in the past from the model of isolated perfused rat kidney in which variables could be changed in a controlled manner and systemic influences could be eliminated. However, reviewing the data from the studies that used this model inspires us to conclude that such model can be a useful tool to probe the undiscovered aspects of the renal actions of CNP and should be advocated for future studies on it.