A study was done to compare plasma disposition kinetics and the fecal elimination profile of doramectin (DRM) after oral or intramuscular (IM) administration in horses. Ten clinically healthy horses, 328-502kg body weight (bw), were assigned to 2 experimental groups of 5 horses each. Group 1 was treated with an oral dose of 0.2mgDRM/kgbw, while Group 2 was treated with 0.2mgDRM/kgbw by IM route. Blood and fecal samples were collected at different times between 0.5h and 60 days post-treatment. After plasma and fecal drug extraction and derivatization, samples were analysed by high performance liquid chromatography (HPLC). A non-compartmental kinetic analysis was performed. Results were expressed as mean±standard deviation and were compared using Mann-Whitney U-test. The parent molecule was detected in plasma between 30min and either 30 (oral) or 60 (IM) days post-treatment. Peak plasma concentrations (Cmax) of 51.6±22.2 and 33.3±10.5ng/mL were obtained after oral administration and IM route, respectively. Differences between administration route were not statistically significant (P=0.42). The value for the area under the concentration-time curve (AUC) was 178.6±53.7 and 393.6±66.6ngday/mL for Group 1 and Group 2, respectively. These differences were significant (P<0.0079). The averages for mean residence time (MRT) values were 7.7±0.9 and 13.2±4.5 days for oral and IM treated groups, respectively. In horses treated using the oral route, the peak fecal concentration (FCmax) was 2295±593ng/g observed at 1.9±0.5 days after oral treatment. Whereas, for those treated by IM route, the FCmax was lower (162±26ng/g) (P<0.0079) and it was observed at 5.6±2.9 days. The results of this study showed that the administration route affects plasma disposition kinetics, bioavailability and fecal elimination of DRM. © 2010 Elsevier B.V.