In the present study we used isolated perfused AV-node of rabbit as an experimental model to determine the effect of various concentrations of extract of C. sativus (A = 9×10⁻², B = 19×10⁻², C = 28×10⁻², D = 37×10⁻² mg L⁻¹) on electrophysiological properties of isolated heart. Selective stimulation protocols were used to independently quantify AV nodal recovery, facilitation and fatigue in 12 rabbits. Our results showed concentration dependent depressant effects of aqueous extract of C. sativus on Wenchebach Cycle Length (WBCL), AV Conduction Time (AVCT), Functional Refractory Periods (FRP). C. sativus (28×10-2 mg L-1) prolonged AVCT from 44.4±5 (control) to 52.2±4 m sec, Rate-dependent properties such as Facilitation and fatigue significantly increased by 19×10⁻² mg L ⁻¹ of C. sativus. In control group magnitude of fatigue was 6.7±0.6 and increased by Saffron to 20±11.5 (p< 0.05). The effect of extract was prominent on fast pathway. The above results indicated differential effects of C. sativus on slow and fast pathways which has a dominant role on the fast pathway. This research for the first time has explained the role of saffron on the protective mechanism of artrioventricular node against supraventricular arrhythmia. These results showed the non-specific effect of saffron on the transitional cells of fast nodal pathway which was manifested as a rate-independent increase of basic and functional (facilitation and fatigue) parameters of artrioventricular node. © 2006 Asian Network for Scientific Information.