This study evaluates the comparative plasma dispositions of ivermectin (IVM) and doramectin (DRM) following oral and subcutaneous administration (200 μg/kg) over a 40-day period in dogs. Twenty bitches were allocated by weight in to four groups (Groups I–IV) of five animals each. Animals in the first two groups (Groups I and II) received orally the injectable solutions of IVM and DRM, respectively, at the dose of 200 μg/kg bodyweight. The other two groups (Groups III and IV) received subcutaneously injectable solutions at the same dose rate. Blood samples were collected between 1 h and 40 days after treatment and the plasma samples were analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The results indicated that IVM produced a significantly higher maximum plasma concentration (Cmax: 116.80 ± 10.79 ng/ml) with slower absorption (tmax: 0.23 ± 0.09 day) and larger area under the concentration versus time curve (AUC: 236.79 ± 41.45 ng day/ml) as compared with DRM (Cmax: 86.47 ± 19.80 ng/ml, tmax: 0.12 ± 0.05 day, AUC: 183.48 ± 13.17 ng day/ml) following oral administration of both drugs; whereas no significant differences were observed on the pharmacokinetic parameters between IVM and DRM after subcutaneous administrations. In addition, subcutaneously given IVM and DRM presented a significantly lower maximum plasma concentration (Cmax: 66.80 ± 9.67 ng/ml and 54.78 ± 11.99 ng/ml, respectively) with slower absorption (tmax: 1.40 ± 1.00 day and 1.70 ± 0.76 day, respectively) and larger area under the concentration versus time curve (AUC: 349.18 ± 47.79 ng day/ml and 292.10 ± 78.76 ng day/ml, respectively) as compared with the oral administration of IVM and DRM, respectively. No difference was observed for the terminal half-lives (t1/2λz) and mean residence times (MRT) of both molecules. Considering the pharmacokinetic parameters, IVM and DRM could be used by the oral or subcutaneous route for the control of parasitic infection in dogs.