Abstract: OBJECTIVE To investigate the effects of trans-resveratrol derivative 3,5,4'-trimethoxystilbene(TMS) on sodium current(I_Na) and potassium current(I_K1) in guinea pig ventricular myocytes, and to investigate the mechanism of cardioprotection. METHODS Single cardiac myocytes were isolated by enzyme, and the effect were assessed by applying whole-cell patch clamp technique. RESULTS TMS(10 μmol·L^-1) was shown to inhibit I_Na of guinea pig ventricular myocytes and acted quickly (about 3 min), and the inhibition ratio was (36.8±5.6)％(P<0.005) in 10 mins, and its effects were reversible completely after a 10 min washout. 1, 3 μmol·L^-1 TMS didn't decrease I_Na. The maximal activating voltage of INa and I_K1 were not changed. For availability, V_1/2 and S were (-87.0±3.3)mV and (4.9±0.3)mV for control and (-96.7±3.5)mV (P<0.001) and (5.4±0.3)mV (P<0.01) in 10 μmol·L^-1 TMS. For activation, V_1/2 were (-38.9±1.4)mV for control and (-47.3±1.3)mV(P<0.001) in 10 μmol·L^-1 TMS, S could not be changed. CONCLUSION TMS can exhibit direct inhibitory effects on I_Na in guinea pig ventricular myocytes, and these effects were reversible completely.