Abstract The aim of the present study was to estimate permeation of doramectin (DOR) into sheep's milk by following its time course in blood plasma and milk. Six Istrian Pramenka sheep in the early lactation period, each having a suckling lamb, were administered DOR in a single subcutaneous dose of 0.2 mg kg −1 body weight. Blood plasma and milk samples were taken from days 1 to 42 following drug administration. Mean maximal DOR concentration observed ( c max ) in ewes’ blood plasma and milk were 22.8 and 31.1 μg l −1 , respectively, at day 3 ( t max ) following drug administration. Mean elimination half-lives ( t 1/2 ) and mean residence times (MRT) were 3.4 and 6.2 days for plasma data and 4.6 and 6.9 days for milk data, respectively. Transfer of DOR residues to suckling lambs was evaluated by determination of DOR concentration time courses in lambs’ blood plasma. Mean maximal DOR concentration 2.1 μg l −1 ( c max ), was observed at 5.5 days ( t max ) following drug administration to ewes, while t 1/2 and MRT were 3.8 and 9.1 days, correspondingly. Mean time in which concentrations fell below the limit of detection was >35 days for ewes’ blood plasma and >37 days for milk, while residual DOR concentration in lambs’ blood plasma fell below the limit of detection on day 20 following drug administration to ewes in only one out of six lambs. DOR extensively permeated into sheep's milk. Mean milk to plasma concentration ratio was 1.4. It was estimated that 1.6% of the DOR dose was excreted into milk and ingested by suckling lambs. As DOR use during lactation is prohibited, its long lasting presence of residues in milk merits proper veterinary sanitary control. The results reported contribute to further understanding of the DOR persistence and excretion patterns in lactating sheep and implementation of evidence-based guidelines to anti parasitic treatment of dairy animals.