This work establishes a simple method for the determination of naltrexone by chemiluminescence (CL) technique. This method is based on the enhancement effect of naltrexone on the weak CL emission raised from reaction between tris(1,10 phenanthroline)ruthenium(II), Ru(phen)3 2+, and cerium(IV) (Ce(IV)). Under the optimum chemical conditions, CL intensity was correlated linearly with concentration of naltrexone in the range of 0.07-13.7 μg mL-1 with a correlation coefficient of 0.9990. The detection limit for this drug was calculated 0.06 μg mL−1 (3:1 signal-to-noise ratio) and the relative standard deviation for 10 repetitive determinations of 1.37 μg mL-1 naltrexone was 5.3 %. The method was applied to the determination of naltrexone in human plasma and the results were in good agreement with the spiked values.