The aim of this study was to evaluate the effect of the topical application of melatonin on osteointegration of dental implants in Beagle dogs 14 days after their insertion. In preparation for subsequent insertion of dental implants, upper and lower premolars and molars were extracted from 12 Beagle dogs. Each mandible received cylindrical screw implants of 3.25 mm in diameter and 10 mm in length. The implants were randomly assigned to the mesial and distal sites on each side of the mandible. Prior to implanting, 1.2 mg lyophylized powdered melatonin was applied to one bone hole at each side of the mandible. None was applied at the control sites. Eight histological sections per implant were obtained for histomorphometric studies. After a 2-wk treatment period, melatonin significantly increased the perimeter of bone that was in direct contact with the treated implants (P < 0.0001), bone density (P < 0.0001), new bone formation (P < 0.0001) and inter-thread bone (P < 0.05) in comparison with control implants. Topical application of melatonin may act as a biomimetic agent in the placement of endo-osseous dental implants.