Objective: To discuss effect of forsythoside A (FTA) on efflux function and mechanism of P-glycoprotein(P-gp) in Caco-2 cell membrane. Method: Caco-2 cell viability was measured by resazurin assay in the presence of FTA at different concentrations.Effects of FTA and verapamil (inhibitor of P-gp) on cellular drug accumulation in caco-2 cells were investigated

rhodamine 123 (R-123) measured by flowcytometer

was selected as fluorescent probe.Caco-2 cell membrane were exposed to FTA with different concentrations and then ATPase activity of P-gp was assayed. Result: Viability of cells treated by FTA (1-80 mg·L-1) was above 90%

difference was not statistically significant by compared with the negative group

which suggested that Caco-2 cells could maintain their viability under these experiment conditions.Fluorescence intensity of FTA significantly increased by comparing with the blank group

Rh-123 accumulation reached maximum levels of (223.43±5.6)% when the concentration of FTA was 80 mg·L-1.FTA treatments decreased P-gp ATPase activity in Caco-2 cell membranes expressing P-gp. Conclusion: FTA can modulate drug efflux by inhibiting P-gp activity in Caco-2 cell membrane.