Heart failure is correlated with attenuation of parasympathetic nervous function and enhanced sympathetic activity. Carvedilol, a thirdgenerationh-blocker, may improve the prognosis of heart failure better than selective β1-blockers. Not all of its effects, however, can be explained by direct actions on the sympathetic nervous system. This study was therefore performed to investigate the possible alterations of muscarinic cholinergic (M)2 receptors and cholinesterase-positive nerves in different regions of the adriamycin-induced failing rat heart, and the potential effects of carvedilol on these M2 receptors and cholinesterase-positive nerves. Karnovsky–Roots histochemical staining combined with point counting methods, and immunochemical streptavidin–biotin complex staining and image analysis were used to test the distribution of cholinesterase-positive nerves and the expression of M2 receptors, respectively. Our results show that the cholinesterasepositive nerve system was downregulated in the adriamycin-induced failing heart group, while the density of M2 receptors was increased in the carvedilol 3- and 10-mg/kg body weight groups, especially in the endocardial tissues of the left-ventricular free wall. It is concluded that upregulation of M2 receptors may be one of the potential mechanisms by which carvedilol exert its action on heart failure.