OBJECTIVES:  Bacopa monniera has been used as Ayurvedic medicine from time immemorial to improve memory and intellect. P-glycoprotein expressed in intestinal epithelia is an important efflux transporter that plays an important role in bioavailability of orally administered drugs. However any modulation in their activity results in altered pharmacokinetics of co-administered P-gp substrate drugs. The aim of this study was to evaluate the dose dependent effect of Bacopa monnieraon intestinal P-gp activity after one week oral administration in male Sprague Dawley rats. METHODS: Modulation in P-gp activity was evaluated by everted gut sac methodology using digoxin (10 µM) as P-gp substrate. Digoxin transported from mucosal to serosal side of intestine was estimated using HPLC-UV method. Transport of Lucifer yellow (5 µM) a cellular integrity marker across intestinal sac was estimated by fluorescent detector. Viability of tissue was assessed by monitoring the increase in ratio of glucose transport. RESULTS:  Bacopa monnierasignificantly inhibited the intestinal P-gp activity by 2.17 (p<0.001), 3.67 (p<0.001) and 5.25 (p<0.001) fold at 15.5, 31 and 62 mg/kg/day dose respectively when compared to control. Tissue integrity was not disturbed and was found to be viable up to 90 minutes. CONCLUSIONS:  Bacopa monniera inhibited the P-gp activity after one week oral administration. Alteration in P-gp mediated pharmacokinetic parameters might be possible.