In our previous work, the 9-(4-chlorophenyloxycarbonyl)-10-methylacridinium triflate ester (CPOCMA) was used as a chemiluminescent substrate for determination of serum arylesterase activity successfully. Based on CPOCMA, a chemiluminescent method was developed for assessing drugs' effect on this enzyme activity. The method was first validated with a UV method based on phenyl acetate by using trinitroglycerine as a model drug. The inhibitory effects of drugs were then exemplified by three anti-inflammatory drugs (including indometacin, aspirin and acetaminophen). It was observed that the serum-mediated CPOCMA hydrolysis slowed down due to addition of the drugs individually. It means that all the three drugs were PON inhibitors. The IC₅₀ values of indometacin, aspirin and acetaminophen were 0.254, 0.564 and 0.656 mmol/L, respectively; and their average inhibitory constants were 0.154, 1.38, and 2.98 mmol/L, respectively. Competitive inhibitory type was observed for all the three drugs by plotting the Lineweaver-Burk curves. According to the kinetics of the hydrolysis, IC₅₀ values, inhibitory constants, and Michaelis constants, the inhibitory abilities of the three drugs were ranked as: indometacin>aspirin>acetaminophen. This chemiluminescent method is especially valuable for evaluation of those drugs which the UV method cannot work for.