Aim The present study was to investigate the protective effects of oxymatrine （OMT） on regulation of the expression of cytosolic phospholipase A2 （cPLA2）,cyclooxygenase-1 （COX-1）,COX-2 and prostacyclin synthase （PGIS） in isoproterenol-induced rat heart failure. Methods Heart failure was induced in Sprague-Dawley rats by 5 mg/kg isoproterenol （ISO） subcutaneous injection for 7 days.The rats,maintained on a normal diet,were randomly divided into five groups given control,oxymatrine （100 mg/kg） alone,ISO and ISO with oxymatrine （100 mg/kg or 50 mg/kg）.In groups of ISO and ISO with oxymatrine （100 mg/kg or 50mg/kg）,saline or oxymatrine was administered orally for 7 days prior to the ISO administration.ISO （5 mg/kg） was administered subcutaneously for 7 days with saline or oxymatrine.In groups of control and oxymatrine （100 mg/kg） alone,saline was administered subcutaneously for 7 days.Serum brain natriuretic peptide （BNP） level,haemodynamic parameters,histopathological variables and expression of protein levels were analysed. Results Oral administration of OMT significantly inhibited ISO-induced heart failure,as evaluated by serum BNP and haemodynamic parameters,and histological examinations.Coadministration of oxymatrine increased myocardial level of COX-2 and PGIS,and inhibited COX-1 expression in ISO-induced heart failure rat.Whereas the protein level for cPLA2 was markedly increased by ISO,OMT exerted no effects on ISO-induced elevated protein cPLA2 expression.Compared with control group,any indexes in sham rats treated with OMT （100 mg/kg） alone were unaltered （all P＞0.05）. Conclusion Our results suggest that the favourable effects of oxymatrine for management of heart failure are probably achieved by regulation of the COX-1,COX-2 and PGIS expression.