Abstract: OBJECTIVE To explore the effects of different drug delivery cycles on the drug tolerance of nitrates by measuring the degree of coronary vascular expansion. METHODS One hundred and twenty patients having coronary heart disease and would get the operation of coronary angiography were divided into 4 groups: intermittent administration group, short-range continued administration group, long-range continued administration group, blank control group. The 1 mg isosorbide dinitrate was injected into coronary artry during coronary arteriography. The proximal diameter of left anterior descending coronary artery(LAD) and left circumflex branch of coronary artery(LCX) were measured before and 2 min after the injection. The expansion degree was calculated to evaluate the drug resistance of the nitrates. RESULTS One-way analysis of variance showed that the expansion degree of LAD and LCX and the average degree in 4 groups were not exactly the same. The expansion degree of long-range continued administration group was obviously lower than those of the intermittent administration group and blank control group(P<0.05 or 0.01). The expansion degree of short-range continued administration group had no obvious difference with the other 3 groups. There was no obvious difference between the blank control group and intermittent administration group. CONCLUSION Long-term use of nitrates (>72 h) will produce a certain amount of drug resistance; short-term continuous use of nitrates may cause the non-significant resistance; intermittent use of nitrates(8-10 h blank a day) can avoid the occurrence of drug resistance significantly.