OBJECTIVES: Iran had one of the highest uses of Diphenoxylate in the world in 2008. About one billion tablets of Diphenoxylate 2.5 mg have been consumed during that year. In the last months of 2008 the ministry of health tried some policies to reduce the consumption. One was rationing in production the other was doubling the price of 10 medicines which likely were abused including Diphenoxylate. This study tries to show the effectiveness of these two interventions by evaluating monthly consumption of Diphenoxylate during recent five years ended to march 2010.  METHODS: Data were gathered from the distributors and wholesalers of this medicine from whole the country. These data were crosschecked with importation data in the ministry of health. We did a time trend analysis on tabulated data.  RESULTS: There are some variations in monthly use of Diphenoxylate but the trend shows a significant decrease after the rationing in production. In 2009 the average consumption has reached to less than 650 millions of tablet, 4 Defined Daily Dose per 1000 Inhabitants per day which shows 36% decrease in comparison with the previous year. In second half of 2009 and first 2 months of 2010 after the second intervention, there is no significant change in the trend.  CONCLUSIONS: Although the high consumption of opiates in Iran is a multi factorial phenomena but this study shows; the first intervention has been able to control the abuse of Diphenoxylate due to the reduction of market supply and decrease in Diphenoxylate’s unofficial promotion. Considerable result wasn’t seen in the second approach. The user price of Diphenoxylate tablet in Iran is too cheap and doubling the price doesn’t work at all. A significant tax mark-up and increasing the price based on label use may affect on affordability of Diphenoxylate’s abuse.