Objectives: The purpose of this study was to assess the anti-inflammatory, analgesic and osteogenic early effects of melatonin on post-extraction sockets ofpatients requiring third molars extraction. Study Design: A randomized, triple-blind clinical trial was made using a split-mouth design. Both lower third molars of 10 patients were extracted and 3 mg of local melatonin or placebo were applied. Concentrations of interleukin-6 and nitrotyrosine were determined on samples of the clot from the socket by independent ELISA tests. Radiographic bone density was evaluated by measuring Hounsfield Units in panoramic and cross sections obtained by digital scanner. Statistycal analysis by Kolmogorov-Smirnov test was performed for ELISA data. Bone density was analyzed by Shapiro-Wilk test. Subsequently t test was applied. P <0.05 was considered to be significant. Results: The concentration of interleukin-6 increased with the application of melatonin without statistically significance (361.32 ± 235.22 pg/ml vs 262.58 ± 233.92 pg/ml). Nitrotyrosine concentrations showed values below to the detectability pattern (<0.001 nM) in Optic Density curve. Bone density in panoramic sections at socket after melatonin application showed no significant difference (561.98 ± 105.92 HU vs 598.82 ± 209.03 HU). In cross sections, bone density in the alveolar region showed no significant difference(377.42 ± 125.67 HU vs 347.56 ± 97.02 HU). Conclusions: Within the limitations of this pilot study, no differences with the application of melatonin were found in terms of the concentration of interleukin-6 and bone density in post-extraction socket of retained mandibular third molars.