A sensitive and reliable method was developed for the detection of doramectin (DRM) in rabbit tissues (muscle, liver, kidney, and fat) by high-performance liquid chromatography with fluorescence detection. The limit of detection and the limit of quantification were 0.36 ng.g(-1) and 1 ng.g(-1), respectively, for all four tissues examined. Mean recoveries ranged from 70.8 to 98.0% for all samples at all fortification levels with a coefficient of variation below 12.1%. The method was further applied to study depletion of DRM residues in rabbits subcutaneously administered a single dose of 0.4 mg.kg(-1) body weight. The highest DRM concentration was measured in fat tissue, indicating that fat is the target tissue for DRM in rabbits. Although the concentrations of DRM residues in all tissues were below the maximum residue limits established by the European Medicines Agency, the Codex Alimentarius Commission, and the Ministry of Agriculture of China for other food-producing species at 16 days posttreatment, the statistically established withdrawal period was calculated to be 23 days.