Autonomic　imbalance　characterized　by　sympathetic　predominance　coinciding　with　diminished　vagal　activity　is　an　independent　risk　factor　in　cardiovascular　diseases.　Several　studies　show　that　vagus　nerve　stimulation　exerted　beneficial　effects　on　cardiac　function　and　survival.　In　this　study,　we　investigated　the　vagomimetic　effect　of　pyridostigmine　on　left　ventricular　(LV)　remodeling　in　rats　after　myocardial　infarction.　After　myocardial　infarction,　surviving　rats　were　treated　with　or　without　pyridostigmine　(31　mg　center　dot　kg(-1)center　dot　d(-1))　for　2　weeks,　and　hemodynamic　parameters　were　measured.　LV　tissue　was　used　to　assess　infarct　size　and　interstitial　fibrosis　by　Masson＇s　trichrome　and　0.1%　picrosirius　red　staining.　Protein　expression　of　heart　tissues　was　used　to　assess　the　efficacy　of　the　treatment.　Pyridostigmine　markedly　reduced　myocardial　infarct　size　and　improved　cardiac　diastolic　function.　These　improvements　were　accompanied　with　a　significant　decrease　in　matrix　metalloproteinase-2　expression　and　collagen　deposition.　Additionally,　pyridostigmine　inhibited　both　transforming　growth　factor-beta　1　(TGF-beta　1)　and　TGF-beta　1-activated　kinase　expression　in　hearts　postmyocardial　infarction.　Thus,　pyridostigmine　reduces　collagen　deposition,　attenuates　cardiac　fibrosis,　and　improves　LV　diastolic　function　after　myocardial　infarction　via　TGF-beta　1/TGF-beta　1-activated　kinase　pathway　inhibition.