To evaluate the effect of chronic exposure to diazinon in the gastrointestinal tract, Caco-2 cells were made resistant by growing in low concentrations of diazinon (0.02 μM) that was gradually increased to 20 μM within 4.5 months. Resistant cells showed significant higher growth in the presence of 15, 45 and 135 μM of diazinon (96.08, 81.80 and 65.16% of control) compared to parent cells (79.71, 71.76 and 29.50% of control, respectively; p < 0.05). P-glycoprotein (P-gp) expression increased significantly in resistant cells (P-gp to beta-actin ratio 0.586 for parent and 1.255 for resistant cells, respectively; p < 0.05) without any alteration in MDR-1 mRNA level (p > 0.05).