The present study was designed to investigate the mechanisms underlying the effects of SO2 on functions of the isolated perfused hearts in rats. The results suggest that both SO2 and SO2 derivatives (sulfite: bisulfite, 3:1, M/M) elicited a negative inotropic effect. At high concentrations, the effects of SO2 or its derivatives on heart functions might be related to the increasing of reactive oxygen species (ROS) contents and decreasing of ATPase activities as well as the potentially damaging effects on the hearts; while at low concentrations, SO2 or its derivatives might modulate heart functions mainly through the NO signal transduction pathway.